To determine the effects of intermittent hypoxemia on daytime sleepiness in the clinical setting of obstructive sleep apnea syndrome, we enrolled seven patients in a prospective, randomized, crossover study. We had two experimental conditions with NCPAP treatment as follow: (1) to correct apneas, sleep fragmentation, and hypoxemia; and (2) to correct apneas and sleep fragmentation and at the same time, induce intermittent hypoxemia. The outcome variable, daytime sleepiness, was measured objectively with the multiple sleep latency test following completion of baseline and each treatment condition. Compared with sleep latencies in the untreated condition, both experimental treatment arms prolonged sleep latencies (p less than 0.05). We found no statistically significant differences between mean MSLT scores obtained after NCPAP treatment under hypoxemic and nonhypoxemic conditions. In summary, two nights of intermittent nocturnal hypoxemia during NCPAP treatment for OSAS did not diminish the objective improvement in daytime somnolence seen with NCPAP treatment in the absence of nocturnal hypoxemia. Results lend further support to the hypothesis relating excessive daytime sleepiness to sleep fragmentation.