Purpose: Postoperative monitoring of circulation and respiration is pivotal to guide intervention strategies and ensure patient outcomes. Transcutaneous blood gas monitoring (TCM) may allow for noninvasive assessment of changes in cardiopulmonary function after surgery, including a more direct assessment of local micro-perfusion and metabolism. To form the basis for studies assessing the clinical impact of TCM complication detection and goal-directed-therapy, we examined the association between clinical interventions in the postoperative period and changes in transcutaneous blood gasses. Methods: Two-hundred adult patients who have had major surgery were enrolled prospectively and monitored with transcutaneous blood gas measurements (oxygen (TcPO₂) and carbon dioxide (TcPCO₂)) for 2 h in the post anaesthesia care unit, with recording of all clinical interventions. The primary outcome was changes in TcPO₂, secondarily TcPCO₂, from 5 min before a clinical intervention versus 5 min after, analysed with paired t-test. Results: Data from 190 patients with 686 interventions were analysed. During clinical interventions, a mean change in TcPO₂ of 0.99 mmHg (95% CI-1.79–0.2, p = 0.015) and TcPCO₂ of−0.67 mmHg (95% CI 0.36–0.98, p < 0.001) was detected. Conclusion: Clinical interventions resulted in significant changes in transcutaneous oxygen and carbon dioxide. These findings suggest future studies to assess the clinical value of changes in transcutaneous PO2 and PCO2 in a postoperative setting. Trial registry: Clinical trial number: NCT04735380. Clinical trial registry: https://clinicaltrials.gov/ct2/show/NCT04735380