Symptoms of CFS include post-exertional malaise; unrefreshing sleep; widespread muscle and joint pain; sore throat; headaches of a type not previously experienced; cognitive difficulties; chronic, often severe, mental and physical exhaustion; and other characteristic symptoms in a previously healthy and active person. Persons with CFS may report additional symptoms including muscle weakness, increased sensitivity to light, sounds and smells, orthostatic intolerance, digestive disturbances, depression, and cardiac and respiratory problems. It is unclear if these symptoms represent co-morbid conditions or are produced by an underlying etiology of CFS.

Fatigue is a common symptom in many illnesses, but CFS is comparatively rare. Estimates of CFS prevalence vary widely, from 7 to 3,000 cases of CFS for every 100,000 adults, but national health organizations have estimated more than 1 million Americans and approximately a quarter of a million people in the UK have CFS. CFS occurs more often in women than men, and is less prevalent among children and adolescents. The quality of life is "particularly and uniquely disrupted" in CFS.

There is agreement on the genuine threat to health, happiness and productivity posed by CFS, but various physicians' groups, researchers and patient advocates promote different nomenclature, diagnostic criteria, etiologic hypotheses and treatments, resulting in controversy about many aspects of the disorder. The name "chronic fatigue syndrome" itself is controversial as many patients and advocacy groups, as well as some experts, believe the name trivializes the medical condition and want the name changed.