CO₂ inhalation has been previously reported as a treatment for central sleep apnea both when associated with heart failure or where the cause is unknown. Here we evaluated a novel CO₂ supply system using a novel open mask capable of comfortably delivering a constantly inspired fraction of CO₂ (FiCO₂) during sleep. We recruited eighteen patients with central sleep apnea (13 patients with cardiac disease, and 5 patients idiopathic) diagnosed by diaphragm EMG recordings made during overnight full polysomnography (Night 1). In each case the optimal FiCO₂ was determined by an overnight manual titration with PSG (Night 2). Titration commenced at 1% CO₂ and increased by 0.2% increments until CSA disappeared. Patients were then treated on the third night (Night 3) with the lowest therapeutically effective concentration of CO₂ derived from night 2. Comparing night 1 and night 3, both AHI (31±14 vs. 6±3 events/h, p<0.01) and arousal index (22±8 vs. 15±8 events/h, p<0.01) were significantly improved during CO₂ treatment. Sleep efficiency improved from 71±18 to 80±11%, p<0.05, and sleep latency was shorter (23±18 vs. 10±10 min, p<0.01). Heart rate was not different between night 1 and night 3. Our data confirm the feasibility of our CO₂ delivery system and indicate that individually titrated CO₂ supplementation with a novel device including a special open mask can reduce sleep disordered breathing severity and improve sleep quality. Randomized controlled studies should now be undertaken to assess therapeutic benefit for patients with CSA.