['This two-part study was designed to determine the effect of supplemental oxygen on the detection of hypoventilation, evidenced by a decline in oxygen saturation (Spo(2)) with pulse oximetry.', 'Phase 1 was a prospective, patient-controlled, clinical trial. Phase 2 was a prospective, randomized, clinical trial.', 'Phase 1 took place in the operating room. Phase 2 took place in the postanesthesia care unit (PACU).', 'In phase 1, 45 patients underwent abdominal, gynecologic, urologic, and lower-extremity vascular operations. In phase 2, 288 patients were recovering from anesthesia.', 'In phase 1, modeling of deliberate hypoventilation entailed decreasing by 50% the minute ventilation of patients receiving general anesthesia. Patients breathing a fraction of inspired oxygen (Fio(2)) of 0.21 (n = 25) underwent hypoventilation for up to 5 min. Patients with an Fio(2) of 0.25 (n = 10) or 0.30 (n = 10) underwent hypoventilation for 10 min. In phase 2, spontaneously breathing patients were randomized to breathe room air (n = 155) or to receive supplemental oxygen (n = 133) on arrival in the PACU.', 'In phase 1, end-tidal carbon dioxide and Spo(2) were measured during deliberate hypoventilation. A decrease in Spo(2) occurred only in patients who breathed room air. No decline occurred in patients with Fio(2) levels of 0.25 and 0.30. In phase 2, Spo(2) was recorded every min for up to 40 min in the PACU. Arterial desaturation (Spo(2) < 90%) was fourfold higher in patients who breathed room air than in patients who breathed supplemental oxygen (9.0% vs 2.3%, p = 0.02).'] Does supplemental oxygen impair detection of hypoventilation by pulse oximetry?