Essential elements of Myalgic Encephalomyelitis (ME) are muscle (weakness) and tenderness, cognitive deficits, neurological impairments, especially of cognitive, autonomic and sensory functions, post-exertional “malaise”: It is a continuous increase of symptoms due to a minor physical and mental exertion. Chronic fatigue Syndrome (CFS) is defined as clinically evaluated, unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of eight specific symptoms, e.g., sore throat, unrefreshing sleep, and headaches. As we know cognitive deficits and post-exertional “malaise” are not necessary for the diagnosis CFS, only part of the CFS patient group meets the diagnostic criteria for ME. So, post-exertional “malaise” is considered to be the distinctive feature of ME. However, “malaise” is an ambiguous and subjective notion. To assess post-exertional malaise objectively, different studies have employed widely used methods to quantify the deviant effects of exertion in ME (CFS).