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Introduction: During robot assisted hysterectomies and prostatectomies, surgical exposure demands the application of a CO2 pneumoperitoneum with a very steep Trendelenburg position (40 degrees). The extent to which oxygenation and ventilation might be compromised intra-operatively remains poorly documented., Methods: Dead-space ventilation and venous admixture were determined in 18 patients undergoing robot assisted hysterectomy (n = 6) or prostatectomy (n = 12). Anesthesia was maintained with desflurane in O2 or O2/air, with the inspired O2 fraction left at the discretion of the attending anesthesiologist. Controlled mechanical ventilation was used, but 15 min after assuming the Trendelenburg position and up until resuming the supine position pressure controlled ventilation was used. Dead-space ventilation and venous admixture were determined using Bohr's formula and Nunn's iso-shunt diagram, respectively, at the following 7 stages of the procedure: 15 min after induction; 5 min after applying the CO2 pneumoperitoneum (intra-abdominal pressure 12 mm Hg) but while still supine; 5, 60, and 120 min after assuming the Trendelenburg positioning; and 5 and 15 min after reassuming the supine position., Results: Venous admixture did not change. Dead-space ventilation increased after Trendelenburg positioning, and returned to baseline values after resuming the supine position. However, individual patterns varied widely., Discussion: The lung has a remarkable yet incompletely understood capacity to withstand the effects of a CO2 pneumoperitoneum and steep Trendelenburg position during general anesthesia. While individual responses vary and should be monitored, effects on dead-space ventilation and venous admixture are small and should not be an obstacle to provide optimal surgical exposure during robot assisted prostatectomy or hysterectomy.