During sleep, none of 9 subjects with chronic obstructive pulmonary disease (COPD) were apneic. Despite ventilation, acute arterial oxygen desaturation of 11% or more occurred in 6 of them. The other 3 were nondesaturators (i.e., 3% or less desaturation) during sleep. The desaturation that occurred in the 6 subjects with COPD was associated with episodes of (1) esophageal pressure or abdominal respiratory movement that acutely decreased in amplitude during rapid-eye-movement (REM) sleep, or (2) esophageal pressure or abdominal respiratory movement that acutely increased in amplitude in association with snoring during non-REM and REM sleep. During daytime wakefulness, ventilatory responses to hypoxia and hypercapnia were markedly less in the 6 desaturators compared with the 3 nondesaturators and 5 healthy control subjects. The decreased ventilatory responses in the 6 desaturators appeared to result from both impaired respiratory mechanical effectiveness and impaired respiratory center responsiveness to chemoreceptor stimulation. We suggest that subjects with COPD with these respiratory impairments are predisposed to develop severe nonapneic oxygen desaturation during the added respiratory impairment of REM sleep or of what appears to be sleep-related partial upper airway obstruction.