Obstructive sleep apnea (OSA) is the result of repeated episodes of upper airway obstruction (UAO) during sleep. Recent evidence indicates that alterations in upper airway anatomy and disturbances in neuromuscular control both play a role in the pathogenesis of obstructive sleep apnea. We hypothesized that subjects without sleep apnea are more capable of mounting vigorous neuromuscular responses to upper airway obstruction than subjects with sleep apnea. To address this hypothesis we lowered nasal pressure to induce upper airway obstruction to the verge of periodic obstructive hypopneas (cycling threshold). Ten patients with obstructive sleep apnea and nine weight-, age-, and sex- matched controls were studied during sleep. Responses in genioglossal EMG (EMG_GG) activity (tonic, peak phasic, and phasic EMG_GG), maximal inspiratory airflow (V_Imax) and pharyngeal transmural pressure (P_TM) were assessed during similar degrees of sustained conditions of upper airway obstruction and compared to those obtained at a similar nasal pressure under transient conditions. Control compared to sleep apnea subjects demonstrated greater EMG_GG, V_Imax, and P_TM responses at comparable levels of mechanical and ventilatory stimuli at the cycling threshold, during sustained compared to transient periods of UAO. Furthermore, the increases in EMG_GG activity in control compared to sleep apnea subjects were observed in the tonic but not the phasic component of the EMG response. We conclude that sustained periods of UAO induce greater increases in tonic EMG_GG, V_Imax, and P_TM in control subjects. Our findings suggest that neuromuscular responses protect individuals without sleep apnea from developing upper airway obstruction during sleep.