The effects of sustained eucapnic hypoxia (SEH, 20 minutes SaO2, approximately 80%) on ventilation and supraglottic airflow resistance (Rua) plus genioglossal (gg) and diaphragmatic (di) electromyograms (EMGs) were compared during wakefulness and nonrapid eye movement (NREM) sleep in six healthy normal male subjects. Early augmentation of ventilation was followed by decline or roll-off in both states. The augmentation of ventilation was less in sleep than wakefulness (e.g., after 5 minutes hypoxia, 140% and 167% of baseline, respectively, p < 0.05). This appeared to be due to three factors: 1) sleep-related increases in Rua [the ventilatory responses to SEH (sleep vs. awake) were inversely related to changes in Rua (sleep vs. awake) (p < 0.05)], 2. reduced central neural drive (inspiratory phasic EMG di after 5 minutes SEH, 111% and 121% of baseline, p < 0.05), and 3) failure to increase respiratory frequency during SEH sleep. There was also a nonsignificant trend to a biphasic response in EMG gg and a small increase in Rua during SEH.