Study Objectives: To use near-infrared spectroscopy to investigate the effect of obstructive sleep apnea on cytochrome oxidase, the terminal enzyme of the mitochondrial respiratory chain. Design: Observational study. Setting: Teaching hospital sleep unit. Patients: Subjects with diagnosed moderate to severe obstructive sleep apnea were recruited from the sleep clinic. Interventions: Subjects were invited to attend 2 daytime sleep-study sessions, which included near-infrared monitoring of cerebral oxygenation and cytochrome-oxidase oxidation state. In addition, in study session 1, full polysomnography was performed (8 subjects, 303 apneas), and in study session 2, arterial oxygen saturation, cerebral blood flow velocity, and blood pressure were monitored (7 subjects, 287 apneas). Measurements and Results: In study session 1, mean (+/-SD) cytochrome-oxidase changes ranged from 0.48 +/- 0.08 muM to 0.13 +/- 0.05 muM. The magnitude of cytochrome-oxidase change correlated significantly with the magnitude of change in the cerebral tissue oxygenation index (P<.001). In study session 2, there were significant correlations between arterial oxygen-saturation changes and cytochrome-oxidase redox changes and between Doppler cerebral blood flow velocity changes and cytochrome-oxidase redox changes (P < .001 and P = .001, respectively). Conclusions: Changes in directly measured cerebral tissue saturation and changes in arterial saturation and cerebral blood flow velocity (the 2 main factors affecting cerebral oxygenation) are associated with changes in cytochrome-oxidase oxidation state. The reduced cerebral oxygenation that occurs during obstructive sleep apnea is associated with changes in the intracellular redox state.