Background This study aimed to evaluate the effects of hypercarbia on arterial oxygenation during one-lung ventilation (OLV). Methods Fifty adult patients undergoing elective video-assisted thoracoscopic lobectomy or pneumonectomy were enrolled. Group I patients (n = 25) were first maintained at normocarbia (PaCO 2 : 38–42 mmHg) for 30 min and then at hypercarbia (45–50 mmHg). In Group II patients (n = 25), PaCO 2 was maintained in the reverse order. Arterial oxygen partial pressure (PaO 2 ), respiratory variables, hemodynamic variables, and hemoglobin concentration were compared during normocarbia and hypercarbia. Arterial O 2 content and O 2 delivery were calculated. Results PaO 2 values during normocarbia and hypercarbia were 66.5 ± 10.6 and 79.7 ± 17.3 mmHg, respectively (mean difference: 13.2 mmHg, 95% CI for difference of means: 17.0 to 9.3, P < 0.001). SaO 2 values during normocarbia and hypercarbia were 92.5 ± 4.8% and 94.3 ± 3.1% (P = 0.009), respectively. Static compliance of the lung (33.0 ± 5.4 vs. 30.4 ± 5.3 ml/cmH 2 O, P < 0.001), arterial O 2 content (15.4 ± 1.4 vs. 14.9 ± 1.5 ml/dl, P < 0.001) and O 2 delivery (69.9 ± 18.4 vs. 65.1 ± 18.1 ml/min, P < 0.001) were significantly higher during hypercarbia than during normocarbia. Conclusions Hypercarbia increases PaO 2 and O 2 carrying capacity and improves pulmonary mechanics during OLV, suggesting that it may help manage oxygenation during OLV. Therefore, permissive hypercarbia may be a simple and valuable modality to manage arterial oxygenation during OLV.