Rationale. Impaired endothelium-dependent vasodilation has been documented in patients with sleep apnea. This impairment may result in blood flow dysregulation during apnea-induced fluctuations in arterial blood gases. Objective. To test the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and cerebral circulation are impaired in patients with sleep apnea. Methods, Measurements and Main Results. In 20 patients with moderate to severe sleep apnea and 20 control subjects, we measured cerebral flow velocity (transcranial Doppler), forearm blood flow (venous occlusion plethysmography), arterial pressure (automated sphygmomanometry), oxygen saturation (pulse oximetry), ventilation (pneumotachograph), and end-tidal oxygen and carbon dioxide tensions (expired gas analysis) during 3 levels of hypoxia and 2 levels of hypercapnia. A subset of 14 patients was restudied after treatment with continuous positive airway pressure. Cerebral vasodilator responses to hypoxia (-0.65±0.44 vs. -1.02±0.72 [mean±SD] units/% saturation, p=0.03) and hypercapnia (2.01±0.88 vs. 2.57±0.89 units/Torr, p=0.03) were smaller in patients vs. controls. Hypoxic vasodilation in the forearm was also attenuated (-0.05±0.09 vs. -0.10±0.09 units/% saturation, p=0.04). Hypercapnia did not elicit forearm vasodilation in either group. Twelve weeks of continuous positive airway pressure treatment enhanced hypoxic vasodilation in the cerebral circulation (-0.83±0.32 vs. -0.46±0.29 units/% saturation, p=0.01) and forearm (-0.19±0.15 vs. -0.02±0.08 units/% saturation, p=0.003), and hypercapnic vasodilation in the brain showed a trend toward improvement (2.24±0.78 vs. 1.76±0.64 units/Torr, p=0.06). Conclusions. Vasodilator responses to chemical stimuli in the cerebral circulation and the forearm are impaired in many patients with OSA. Some of these impairments can be improved with continuous positive airway pressure.