BACKGROUND Morbidly obese patients are more prone to desaturation of arterial blood during apnea with induction of anesthesia than are non-obese. This study aimed to assess the effect of low-pressure continuous positive airway pressure (CPAP) with pressure support ventilation (PSV) during pre-oxygenation on partial oxygen pressure in arterial blood (PaO2 ) immediately after tracheal intubation (post-intubation PaO2). METHODS Forty-four adult patients scheduled for laparoscopic gastric bypass surgery were pre-oxygenated with 80% O2 for 2 min, randomized either to CPAP 5 cm H2O + PSV 5 cm H2O (CPAP/PSV, n = 22) or neutral-pressure breathing without CPAP/PSV (control, n = 22). Anesthesia was induced in a rapid-sequence protocol and the trachea was intubated without prior mask ventilation. Arterial blood gases were measured before pre-oxygenation, before induction of anesthesia, and immediately following intubation, before the first positive pressure breath. RESULTS After pre-oxygenation, partial carbondioxide pressure was significantly lower in the CPAP/PSV group (4.9 ± 0.5 kPa), (mean ± standard deviation) than in the control group (5.2 ± 0.7 kPa) (P = 0.025). Post-preoxygenation PaO2 did not differ between the groups, but post-intubation PaO2 was significantly higher in the CPAP/PSV group (32.2 ± 4.1 kPa) than in the control group (23.8 ± 8.8 kPa) (P < 0.001). In the control group, nadir oxygen saturation was lower (median 98%, range 83-99%) than in the CPAP/PSV group (median 99%, range 97-99%, P = 0.011). CONCLUSIONS In morbidly obese patients, low-pressure CPAP combined with low-pressure PSV during pre-oxygenation resulted in better oxygenation, compared with neutral-pressure breathing, and prevented desaturation episodes.