Several studies provided evidence for generalized hyperalgesia in fibromyalgia or whiplash-associated disorders. In chronic fatigue syndrome, however, pain is a frequently reported complaint, but up to now, evidence for generalized hyperalgesia is lacking. The aim of this study is to examine whether the pressure pain thresholds (PPTs) at both symptomatic and asymptomatic sites differ in chronic fatigue syndrome (CFS) patients with chronic pain, compared to healthy controls. Therefore, 30 CFS patients with chronic pain and 30 age- and gender-matched healthy controls indicated on a Margolis Pain Diagram where they felt pain lasting longer than 24 h in the past 4 weeks. After completing a test battery of questionnaires evaluating pain cognitions, functional status and symptomatology, a blinded researcher assessed PPTs bilaterally at seven nonspecific sites on both trunk and extremities. PPTs were compared for the two complete groups. In addition, PPTs of patients and controls who did not report pain in a respective zone were compared. PPTs of the patients were significantly lower (p