ABSTRACT Background Optimizing perioperative management strategies to promote the rapid recovery remains a focus and challenge research. Normobaric hyperoxia enhances antioxidant defenses and promotes tissue repair, improving functional outcomes in stroke patients. This study aimed to investigate the influence of perioperative normobaric hyperoxia combined with pulmonary rehabilitation on video‐assisted thoracoscopic surgery‐treated lung cancer patients. Methods This trial enrolled 100 patients with pulmonary nodules scheduled for video‐assisted thoracoscopic surgery (VATS). Eligible patients were randomized in a 1:1 ratio into two groups. The primary outcomes were postoperative length of stay (LOS) and total hospitalization costs. Secondary outcomes included incidence of postoperative pulmonary complications (PPCs), postoperative inflammatory indicators, activities of daily living (ADL), perioperative outcomes, and readmission rates within 30 days and 6 months after discharge. Results Eighty‐four patients completed the study. The intervention group experienced a significantly shorter postoperative LOS (2 days, IQR 1.8 to 3) and lower total hospitalization cost (41 185 RMB, IQR 35094 to 47 028). The intervention group reported better scores of ADL on postoperative (45 points, IQR 33.8 to 55) and discharge (95 points, IQR 90 to 100). But there were no differences in the incidence of PPCs, C‐reactive protein, procalcitonin, perioperative outcomes, and readmission rates within 30 days and 6 months after discharge. Conclusions Normobaric hyperoxia combined with perioperative pulmonary rehabilitation may reduce postoperative LOS and decreased costs for VATS‐treated lung cancer patients. This approach expected to optimize outcomes and improve rehabilitation for early‐stage lung cancer patients. Trial Registration: The clinical trial was registered on January 17, 2018, with the registration number ChiCTR1800014512
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