This study used a brief battery of neuropsychological measures to examine the performance of patients with chronic fatigue syndrome (CFS) (N = 16) and patients in a major depressive episode (N = 23). The overall neuropsychological performance of the CFS group was not significantly different from depressed patients, and both groups scored within normal limits on most measures. Variability of neuropsychologic performance was in general unrelated to level of depressive symptoms. The results are discussed in terms of the validity of the cognitive criterion for the CFS diagnosis. Subjective complaints of cognitive dysfunction by CFS patients in light of the lack of objective evidence for the same are considered in terms of a somatic vigilance hypothesis.