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To determine the effect of submaximal steady-state exercise on cognitive performance in patients with chronic fatigue syndrome (CFS) alone, CFS with comorbid fibromyalgia FM (CFS+FM), and sedentary healthy controls (CON).Twenty CFS-only patients, 19 CFS+FM, and 26 CON completed a battery of cognitive tests designed to assess speed of information processing, variability, and efficiency. Tests were performed at baseline, immediately before, and twice following 25 min of either cycle ergometry set at 40% of peak oxygen capacity or quiet rest.There were no group differences in average percentage of peak oxygen consumption during exercise (CFS = 45%; CFS+FM = 47%; Control = 43%: P = 0.2). There were no significant effects of acute exercise on cognitive performance for any group. At baseline, one-way ANOVA indicated that CFS patients displayed deficits in speed of processing, performance variability, and task efficiency during several cognitive tests compared with healthy controls. However, the CFS+FM patients were not different than controls. Repeated measures ANOVA indicated that across all tests (pre- and postexercise) CFS, but not CFS+FM, were significantly less consistent (F2,59 = 3.7, P = 0.03) and less efficient (F2,59 = 4.6, P = 0.01) than controls.CFS patients without comorbid FM exhibit subtle cognitive deficits in terms of speed, consistency, and efficiency that are not improved or exacerbated by light exercise. Importantly, our data suggest that CFS+FM patients do not exhibit cognitive deficits either pre- or postexercise. These results highlight the importance of disease heterogeneity in studies determining acute exercise and cognitive function in CFS.