Merck Manual

Please confirm that you are not located inside the Russian Federation

honeypot link

Chronic Fatigue Syndrome

(Systemic Exertion Intolerance Disease; SEID; Myalgic Encephalomyelitis; ME/CFS)


Stephen Gluckman

, MD, Perelman School of Medicine at The University of Pennsylvania

Reviewed/Revised Jul 2023

Chronic fatigue syndrome, also called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), refers to long-standing severe and disabling fatigue without a proven physical or psychological cause and without objective abnormalities found on physical examination or laboratory testing.

  • Unexplained fatigue lasts for 6 consecutive months or longer.

  • Sometimes symptoms begin during or after an illness that resembles a viral infection.

  • Treatments include relieving symptoms, cognitive-behavioral therapy, and graded exercise.

Although as many as 25% of people report being chronically fatigued Fatigue Fatigue is when a person feels a strong need to rest and has so little energy that starting and sustaining activity is difficult. Fatigue is normal after physical exertion, prolonged stress... read more , only 0.5% of people (1 in 200) have chronic fatigue syndrome. Chronic fatigue syndrome affects people primarily between the ages of 20 and 50 and is more often described among young and middle-aged women than men, although it has been noted in people of all ages, including children. People with chronic fatigue syndrome have real and often disabling symptoms. Chronic fatigue syndrome is not the same as pretending to have symptoms (a disorder known as malingering).

Causes of Chronic Fatigue Syndrome

Despite considerable research, the cause of chronic fatigue syndrome remains unknown. Controversy exists as to whether there is a single cause or many causes and whether the cause is physical or mental, but either way the symptoms are very real to the person.

Some researchers believe the syndrome ultimately will prove to have several causes, including genetic predisposition and exposure to microbes, toxins, and other physical and emotional factors.

Infectious diseases

Some people who have recovered from COVID-19 infection COVID-19 COVID-19 is an acute respiratory illness that can be severe and is caused by the coronavirus named SARS-CoV-2. Symptoms of COVID-19 vary significantly. Two types of tests can be used to diagnose... read more are "long-haulers" with persistent symptoms. Some of these symptoms are the result of organ damage from the infection and/or treatment, and others may be from post-traumatic stress disorder (PTSD) Posttraumatic Stress Disorder (PTSD) Posttraumatic stress disorder (PTSD) involves intense, unpleasant, and dysfunctional reactions after an overwhelming traumatic event. Events that threaten death or serious injury can cause intense... read more . In addition, in some people, COVID-19 seems to trigger typical chronic fatigue syndrome. Currently, there are limited data and information about the long-term effects of COVID-19, so further studies are needed to determine whether some people with delayed recovery develop chronic fatigue syndrome.

Immunologic abnormalities

Some minor abnormalities of the immune system Overview of the Immune System The immune system is designed to defend the body against foreign or dangerous invaders. Such invaders include Microorganisms (commonly called germs, such as bacteria, viruses, and fungi) Parasites... read more are possible. They can collectively be called immune system dysregulation. However, no abnormalities are specifically characteristic of the disorder. People with chronic fatigue syndrome do not have a medically serious problem with their immune system. People with chronic fatigue syndrome are not immunocompromised and are not at increased risk for infections. No evidence indicates that allergies are the cause, although about 65% of people with chronic fatigue syndrome report previous allergies. No hormonal abnormalities or mental health disorders have been shown to cause chronic fatigue syndrome.

Genetic and environmental factors

Chronic fatigue syndrome seems to run in families, possibly supporting a genetic component or an environmental trigger. Alternatively, members of the same family may respond similarly to physical and psychosocial stress and/or may have been exposed to the same substances.

Symptoms of Chronic Fatigue Syndrome

Most people who have chronic fatigue syndrome are successful and function at a high level until the disorder begins, usually abruptly, often following a stressful event. The main symptom is fatigue that usually lasts at least 6 months and is severe enough to interfere with daily activities. Severe fatigue is present even on awakening and persists throughout the day. The fatigue often worsens with physical exertion or during periods of psychological stress. However, physical evidence of muscle weakness or of joint or nerve abnormalities is absent. Extreme fatigue may begin during or after recovery from an illness that resembles a viral infection, with a fever, runny nose, and tender or painful lymph nodes. However, in many people, fatigue begins without any such preceding illness.

Other symptoms that may occur are difficulty concentrating and sleeping, sore throat, headache, joint pains, muscle pains, and abdominal pain. Depression is common, particularly when symptoms are severe or worsening. Symptoms often overlap with those of fibromyalgia Fibromyalgia Fibromyalgia is characterized by poor sleep, fatigue, mental cloudiness, and widespread aching and stiffness in soft tissues, including muscles, tendons, and ligaments. Poor sleep, stress, strains... read more , a possibly related disorder.

Diagnosis of Chronic Fatigue Syndrome

  • Laboratory tests to exclude other causes of symptoms

No laboratory tests are available to confirm a diagnosis of chronic fatigue syndrome. Doctors therefore must rule out other diseases that may cause similar symptoms. Sometimes doctors do tests to rule out disorders such as anemia Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more , electrolyte abnormalities Overview of Electrolytes More than half of a person's body weight is water. Doctors think about water in the body as being restricted to various spaces, called fluid compartments. The three main compartments are Fluid... read more , kidney failure Overview of Kidney Failure Kidney failure is the inability of the kidneys to adequately filter metabolic waste products from the blood. Kidney failure has many possible causes. Some lead to a rapid decline in kidney function... read more , inflammatory disorders (such as rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is an inflammatory arthritis in which joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and often destruction of joints.... read more Rheumatoid Arthritis (RA) ), sleep disorders Overview of Sleep Sleep is necessary for survival and good health, but why sleep is needed and exactly how it benefits people are not fully understood. One of sleep's benefits is its restorative effect on people's... read more , or thyroid Overview of the Thyroid Gland The thyroid is a small gland, measuring about 2 inches (5 centimeters) across, that lies just under the skin below the Adam’s apple in the neck. The two halves (lobes) of the gland are connected... read more or adrenal gland disorders Overview of the Adrenal Glands The body has two adrenal glands, one near the top of each kidney. They are endocrine glands, which secrete hormones into the bloodstream. Each adrenal gland has two parts. Medulla: The inner... read more . The diagnosis of chronic fatigue syndrome is made only if no other cause, including side effects of medications, is found to explain the fatigue and other symptoms.

In 2015, the Institute of Medicine (now the Health and Medicine Division of The National Academies of Sciences, Engineering, and Medicine) proposed a new name for this disorder, systemic exertion intolerance disease (SEID). They also affirmed the validity of this debilitating disorder and simplified the criteria for diagnosis. The criteria require that the person have the following 3 symptoms:

  • A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities that lasts for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially relieved by rest

  • Symptoms worsened with physical activity

  • Unrefreshing sleep

At least one of the following manifestations is also required:

  • Difficulty thinking

  • Feeling of light-headedness or dizziness when standing up that is relieved by lying down

The frequency and severity of the symptoms should be assessed by a doctor. If people do not have these symptoms at least half of the time with moderate, substantial, or severe intensity, doctors reconsider the diagnosis of chronic fatigue syndrome.

Criteria for diagnosis are important mainly because they help doctors communicate clearly with each other when they study a problem. However, when treating a specific individual, doctors focus more on that person's symptoms rather than the criteria.

Treatment of Chronic Fatigue Syndrome

  • Cognitive-behavioral therapy

  • Graded exercise

  • Medications for depression, sleep, or pain if indicated

In most cases, symptoms of chronic fatigue syndrome lessen over time. However, it often takes years for symptoms to subside, and not all symptoms disappear. People may recover more fully if they focus more on what function they can recover than on how much function they have lost.

Specific symptoms such as pain, depression, and poor sleep are treated. Cognitive-behavioral therapy and gradual graded exercise, which have helped some people, may be worth trying.

Cognitive-behavioral therapy

Cognitive-behavioral therapy is usually a brief course of psychotherapy aimed at redirecting discouraging thoughts that could prevent the positive outlook that can help recovery.

Graded exercise

Excessive periods of prolonged rest cause deconditioning and may actually worsen symptoms of chronic fatigue syndrome. Gradual introduction of regular aerobic exercise, such as walking, swimming, cycling, or jogging, under close medical supervision (called a graded exercise program) may reduce fatigue and improve physical function. Formal, structured physical rehabilitation programs may be best.

Medication and alternative therapies

Specific chronic fatigue syndrome symptoms such as pain, depression, and poor sleep are treated.

Many different medications and alternative therapies have been tried to relieve the chronic fatigue itself. Although many treatments, such as antidepressants and corticosteroids, seem to make a few people feel better, none are clearly effective for all. It can be hard for people and doctors to tell which treatments work because symptoms are different in different people and because symptoms may come and go on their own.

Controlled clinical trials, which compare the benefits of a medication to those of a placebo (a substance that is made to resemble a medication but that does not contain an active ingredient), are the best way to test therapies, and no medication therapy has been shown to be effective for the treatment of chronic fatigue syndrome in controlled trials. A number of treatments directed at possible causes, including use of interferons, intravenous injections of immune globulin, and antiviral medications, have been mostly disappointing and potentially dangerous. Dietary supplements, such as evening primrose oil, fish oil supplements, and high-dose vitamins, are commonly used, but their benefits remain unproved. Other alternative treatments (for example, essential fatty acids, animal liver extracts, exclusion diets, and removal of dental fillings) have also been ineffective. Treatments that have no proven benefits are best avoided because they can have side effects.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Lovaza, Omacor, Triklo
quiz link

Test your knowledge

Take a Quiz!