The purpose of this study was to determine whether chronic fatigue syndrome (CFS) is associated with reduced blood flow and muscle oxidative metabolism. Patients with CFS according to Centers for Disease Control criteria (n = 19) were compared with normal sedentary subjects (n = 11). Muscle blood flow was measured in the femoral artery with Doppler ultrasound after exercise. Muscle metabolism was measured in the medial gastrocnemius muscle with (31)P-magnetic resonance spectroscopy. Muscle oxygen saturation and blood volume were measured using near-infrared spectroscopy. CFS and controls were not different in hyperemic blood flow or phosphocreatine recovery rate. Cuff pressures of 50, 60, 70, 80, and 90 mmHg were used to partially restrict blood flow during recovery. All pressures reduced blood flow and oxidative metabolism, with 90 mmHg reducing blood flow by 46% and oxidative metabolism by 30.7% in CFS patients. Hyperemic blood flow during partial cuff occlusion was significantly reduced in CFS patients (P < 0.01), and recovery of oxygen saturation was slower (P < 0.05). No differences were seen in the amount of reduction in metabolism with partially reduced blood flow. In conclusion, CFS patients showed evidence of reduced hyperemic flow and reduced oxygen delivery but no evidence that this impaired muscle metabolism. Thus CFS patients might have altered control of blood flow, but this is unlikely to influence muscle metabolism. Furthermore, abnormalities in muscle metabolism do not appear to be responsible for the CFS symptoms.