Objectives: Ventilatory after-discharge (sustained elevation of ventilation following stimulus removal) occurs during sleep but not when hypocapnia is present. Genioglossus after-discharge also occurs during sleep, but CO2 effects have not been assessed. The relevance is that postarousal after-discharge may protect against upper airway collapse. This study aimed to determine whether arousal elicits genioglossus after-discharge that persists into sleep, and whether it is influenced by CO2. Methods: Twenty-four healthy individuals (6 female) slept with a nasal mask and ventilator. Sleep (EEG, EOG, EMG), ventilation (pneumotachograph), end-tidal CO2 (P-ET CO2), and intramuscular genioglossus EMG were monitored. NRE Meucapnia was determined during 5 minutes on continuous positive airway pressure (4 cmH(2) O). Inspiratory pressure support was increased until P-ET CO2 was >= 2 mm Hg below NREM eucapnia. Supplemental CO2 was added to reproduce normocapnia, without changing ventilator settings. Arousals were induced by auditory tones and genioglossus EMG compared during steady-state hypocapnia and normocapnia. Results: Eleven participants (4 female) provided data. Prearousal P-ET CO2 was less (p < .05) during hypocapnia (40.74 +/- 2.37) than normocapnia (43.82 +/- 2.89), with differences maintained postarousal. After-discharge, defined as an increase in genioglossus activity above prearousal levels, occurred following the return to sleep. For tonic activity, after-discharge lasted four breaths irrespective of CO2 condition. For peak activity, after-discharge lasted one breath during hypocapnia and 6 breaths during normocapnia. However, when peak activity following the return to sleep was compared between CO2 conditions no individual breath differences were observed. Conclusions: Postarousal genioglossal after-discharge may protect against upper airway collapse during sleep. Steady-state CO2 levels minimally influence postarousal genioglossus after-discharge.