Chronic fatigue syndrome (CFS) is a disabling disease with unknown etiology. There is accumulating evidence of altered cardiovascular autonomic responses to different somatic stressors, in particular orthostatic stress, whereas autonomic responses to mental stress remain to be investigated. In this study, we explored cardiovascular autonomic responses to a simple mental stress test in CFS patients and healthy controls.A consecutive sample of 13 patients with CFS, aged 12 to 18 years, and a volunteer sample of 53 healthy control subjects of equal age and gender distribution were included. Blood pressure, heart rate and acral skin blood flow were continuously recorded during an arithmetic exercise.At baseline, heart rate was significantly higher among CFS patients than controls (p = 0.02). During the arithmetic exercise, however, there were no significant differences in the responses between the two groups.In conclusion, CFS patients have unaltered autonomic responses to simple mental stress as compared to healthy control subjects.