As part of a six-center clinical trial of the effectiveness of continuous v nocturnal oxygen in the management of hypoxemic chronic obstructive pulmonary disease (COPD), we performed detailed neuropsychologic assessments of these patients prior to their beginning treatment. The 203 patients (age, 65 years; Pao2, 51 mm Hg; forced expiratory volume in 1 s, 0.74 L) performed significantly worse than controls on virtually all neuropsychologic tests. Moderate to severe test impairment suggestive of cerebral dysfunction was found in 42% of the patients, as compared with 14% of controls. Higher cognitive functions (abstracting ability, complex perceptual-motor integration) were most severely affected, although half the patients also showed decrements in motor speed, strength, and coordination. Low-order significant inverse correlations were found between neuropsychologic impairment and Pao2, resting arterial oxygen saturation and hemoglobin levels and maximum work. It is concluded that cerebral disturbance is common in hypoxemic COPD and may be related in part to decreased availability of oxygen to the brain.