Corticomotor excitability of peripheral muscles appears to be altered in patients with obstructive sleep apnea. However, there is no evidence of such alteration for upper airway/respiratory muscles that are involved in the pathophysiology of this disease. The aim of this study was to compare the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor excitability in awake healthy subjects versus patients with obstructive sleep apnea. Corticomotor excitability was assessed by transcranial magnetic stimulation in 12 untreated apneic men (48 ± 10 years; body mass index = 28.9 ± 4.7 kg m−2; apnea–hypopnoea index = 41 ± 23 events per hour) and nine control men (45 ± 10 years; body mass index = 27.3 ± 3.3 kg m−2; apnea–hypopnoea index = 7 ± 4 events per hour). Assessments included diaphragm and genioglossus expiratory motor thresholds, and transcranial magnetic stimulation-induced motor-evoked potential characteristics obtained while breathing room air or 5% CO2 (random order) and then 7% CO2 both balanced with pure O2. Transcranial magnetic stimulation twitches were applied during early inspiration and end expiration. Diaphragm motor-evoked potential amplitudes increased and expiratory diaphragm motor-evoked potential latencies decreased during CO2-induced increase in ventilatory drive, with no difference in these responses between patients with obstructive sleep apnea and control subjects. Expiratory genioglossus motor-evoked potential amplitudes were significantly lower in patients with obstructive sleep apnea than in control subjects. Baseline activity of the genioglossus increased with increasing FiCO2, this effect being significantly higher in patients with obstructive sleep apnea than in control subjects. However, neither genioglossus motor-evoked potential amplitudes nor latencies were significantly modified with increasing FiCO2 both in patients with obstructive sleep apnea and in control subjects. Corticomotor excitability of genioglossus and diaphragm are not altered during CO2-induced increase in ventilatory drive in patients with obstructive sleep apnea.