Merck Manual

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Michael R. Wasserman

, MD, California Association of Long Term Care Medicine

Reviewed/Revised Feb 2023
Topic Resources

Fatigue is difficulty initiating and sustaining activity due to a lack of energy and accompanied by a desire to rest. Fatigue is normal after physical exertion, prolonged stress, and sleep deprivation.

Fatigue occurs most often as part of a symptom complex, but even when it is the sole or main presenting symptom, fatigue is one of the most common symptoms.

Patients may refer to certain other symptoms as fatigue; differentiating between them and fatigue is usually, but not always, possible with detailed questioning.

Fatigue can be classified in various temporal categories, such as the following:

  • Recent fatigue: < 1 month duration

  • Prolonged fatigue: 1 to 6 months duration

  • Chronic fatigue: > 6 months duration


  • 1. Wong TL, Weitzer DJ. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas). 2021;57(5):418. Published 2021 Apr 26. doi:10.3390/medicina57050418

Etiology of Fatigue

Most serious (and many minor) acute and chronic illnesses produce fatigue. However, many of these have other more prominent manifestations (eg, pain, cough, fever, jaundice) as the presenting complaint. This discussion focuses on disorders that can manifest primarily as fatigue.

The most common disorders manifesting predominantly as recent fatigue (lasting < 1 month) are

The most common causes manifesting predominantly as prolonged fatigue (lasting 1 to 6 months) are

The most common causes manifesting predominantly as chronic fatigue (lasting > 6 months) are

Several factors commonly cause or contribute to a chief complaint of fatigue, usually prolonged or chronic fatigue (see table ).


Evaluation of Fatigue

Fatigue can be highly subjective. Patients vary in what they consider to be fatigue and how they describe it. There are also few ways to objectively confirm fatigue or tell how severe it is. History and physical examination focus on identifying subtle manifestations of underlying illness (particularly infections, endocrine and rheumatologic disorders, anemia, and depression) that can be used to guide testing.


History of present illness includes open-ended questions about what "fatigue" is, listening for descriptions that could suggest dyspnea on exertion, somnolence, or muscle weakness. The relationships between fatigue, activity, rest, and sleep should be elicited, as should the onset, time course and pattern, and factors that increase or decrease fatigue.

Review of systems should be thorough because potential causes of fatigue are so numerous and diverse. Among important nonspecific symptoms are fever, weight loss, and night sweats (possibly suggesting cancer, a rheumatologic disorder, or an infection). Menstrual history is obtained in women of child-bearing age. Unless a cause is evident, patients should be asked questions from screening questionnaires for psychologic disorders (eg, depression, anxiety, drug use disorder, somatoform disorders, domestic violence).

Past medical history should address known disorders. Complete drug use history should include prescription, over-the-counter, and recreational drugs.

Social history should elicit descriptions of diet, drug use, and the effect of fatigue on quality of life, employment, and social and family relationships.

Physical examination

Vital signs are checked for fever, tachycardia, tachypnea, and hypotension.

General examination should be particularly comprehensive, including general appearance and examination of the heart, lungs, abdomen, head and neck, breasts, rectum (including prostate exam and testing for occult blood), genitals, liver, spleen, lymph nodes, joints, and skin.

Neurologic examination should include testing of, at a minimum, mental status, cranial nerves, mood, affect, strength, muscle bulk and tone, reflexes, and gait.

Usually if fatigue is of recent onset, a more focused examination will reveal the cause. If fatigue is chronic, examination is unlikely to reveal a cause; however, thorough physical examination is an important way to build rapport with the patient and occasionally is diagnostically helpful.

Red flags

  • Chronic weight loss

  • Chronic fever or night sweats

  • Generalized lymphadenopathy

  • Muscle weakness or pain

  • Serious nonfatigue symptoms (eg, hemoptysis, hematemesis, severe dyspnea, ascites, confusion, suicidal ideation)

  • Involvement of > 1 organ system (eg, rash plus arthritis)

  • New or different headache or loss of vision, particularly with muscle pains, in an older adult

Interpretation of findings

In general, a cause is more likely to be found when fatigue is one of many symptoms than when fatigue is the sole symptom. Fatigue that worsens with activity and lessens with rest suggests a physical disorder. Fatigue that is present constantly and does not lessen with rest, particularly with occasional bursts of energy, may indicate a psychologic disorder.

In the absence of red flag findings, a thorough history, physical examination, and routine laboratory testing (plus tests directed at specific findings—see ) should suffice for an initial evaluation. If test results are negative, watchful waiting is usually appropriate; if fatigue worsens or other symptoms and signs develop, the patient is reevaluated.

Several causes can be considered for patients with prolonged or chronic fatigue and selected other common or specific clinical findings.



Testing is directed at causes suspected based on clinical findings. If no cause is evident or suspected based on clinical findings, laboratory testing is unlikely to reveal a cause. Still, many clinicians recommend testing with the following:

  • Complete blood count (CBC)

  • Ferritin

  • Erythrocyte sedimentation rate (ESR)

  • Thyroid-stimulating hormone (TSH)

  • Chemistries, including electrolytes, glucose, calcium, and renal and liver tests

Treatment of Fatigue

Treatment to lessen fatigue is directed at the cause.

Patients with myalgic encephalomyelitis/systemic exertion intolerance disease/chronic fatigue syndrome Chronic Fatigue Syndrome Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS]) is a syndrome of life-altering fatigue lasting > 6 months that is unexplained and is accompanied... read more and idiopathic chronic fatigue are treated similarly. They should be told clearly that the etiology is presently unknown. Treatment is more often successful if the practitioner is patient and nonjudgmental and acknowledges the real effects of fatigue.

Potential treatments include physical therapy (eg, graded exercise therapy) and psychologic support (eg, cognitive-behavioral therapy). Focusing on improving sleep and relieving pain may also help. Goals include returning to work and maintaining normal activity levels.

Geriatrics Essentials: Fatigue

Fatigue is more often the first symptom of a disorder in older patients. For example, the first symptom of pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more in an older woman may be fatigue rather than pulmonary symptoms. The first symptom of other disorders, such as giant cell arteritis Giant Cell Arteritis Giant cell arteritis involves predominantly the thoracic aorta, large arteries emerging from the aorta in the neck, and extracranial branches of the carotid arteries. Symptoms of polymyalgia... read more , may also be fatigue in an older patient. Because serious illness may become apparent soon after sudden fatigue in older patients, the cause should be determined as quickly as possible. Fatigue is also somewhat more likely to be caused by giant cell arteritis or another serious physical disorder in older adults.

Key Points

  • Fatigue is a common symptom.

  • Fatigue caused primarily by a physical disorder usually increases with activity and lessens with rest.

  • Laboratory testing is low yield in the absence of suggestive clinical findings.

  • Successful treatment is more likely if the practitioner is patient and understanding.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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