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Study Objective: While supplemental O 2 inhalation corrects hypoxemia, its effect on post-anesthesia ventilation remains unknown. This pilot trial tested the hypothesis that hyperoxia increases the time spent with a transcutaneous PCO 2 (TcPCO 2 ) > 45 mmHg, compared with standard O 2 supplementation., Design: Single-blinded, parallel two-arm randomized pilot trial., Setting: University hospital., Patients: 20 patients undergoing robotic-assisted laparoscopic nephrectomy., Measurements: After institutional approval and informed consent, patients were randomized to receive O 2 titrated to arterial saturation (SpO 2 ): 90-94% (Conservative O 2 , N =10), or to SpO 2  > 96% (Liberal O 2 , N = 10) for up to 90 min after anesthesia. Continuous TcPCO 2 , respiratory inductance plethysmography (RIP), and SpO 2 , were recorded. We calculated the percentage of time at TcPCO 2  > 45 mmHg for each patient and compared the two groups using analysis of covariance, adjusting for sex, age, and body mass index. We also estimated the sample size required to detect the between-group difference observed in this pilot trial. RIP signals were used to calculate apnea/hypopnea index (AHI), which was then compared between two groups., Main Results: The mean percentage of time with a TcPCO 2  > 45 mmHg was 80.6% for the Conservative O 2 (N=9) and 61.2% for the Liberal O 2 (N=10) group [between-group difference of 19.4% (95% CI: -18.7% to 57.6%), P = 0.140]. With an observed effect size of 0.73, we estimated that 30 participants per group are required, to demonstrate this difference with a power of 80% at a two-sided alpha of 5%. Means SpO 2 were 94.5% and 99.9% for the Conservative O 2 and the Liberal O 2 groups, respectively. AHI was significantly higher in the Conservative O 2 , compared with the Liberal O 2 group (median AHI: 16 vs. 3; P = 0.0014)., Conclusions: Hyperoxia in the post-anesthesia period reduced the time spent at TcPCO 2  > 45 mmHg and significantly decreased AHI, while mean SpO 2 ranged inside the a priori defined limits., Trial Registration: ClinicalTrials.gov identifier: NCT04723433., Competing Interests: Declaration of Competing Interest None of the authors has any competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)