Background: Improving tissue perfusion can improve clinical outcomes in surgical patients, where monitoring may aid clinicians in detecting adverse conditions and guide interventions. Transcutaneous monitoring (TCM) of oxygen (tcpO₂) and carbon dioxide (tcpCO₂) is a well-proven technology and could potentially serve as a measure of local circulation, perfusion and metabolism, but the clinical use is not thoroughly explored. The purpose of this proof-of-concept study was to investigate whether TCM of blood gasses could detect changes in perfusion during major vascular surgery. Methods: Ten patients with peripheral arterial disease scheduled for lower limb major arterial revascularization under general anaesthesia were consecutively included. TcpO₂ and tcpCO₂ were continuously recorded from anaesthesia induction until skin closure with a TCM monitor placed on both legs and the thorax. Peripheral oxygen saturation was kept ≥94% and mean arterial blood pressure ≥65 mmHg. The primary outcomes were changes in tcpO₂ and tcpCO₂ related to arterial clamping and declamping during the procedure and analyzed by paired statistics. Results: Femoral artery clamping resulted in a significant decrease in tcpO₂ (−2.1 kPa, IQR-4.2; −0.8), p=.017)), followed by a significant increase in response to arterial declamping (5.5 kPa, IQR 0–7.3), p=.017)). Arterial clamping resulted in a statistically significant increase in tcpCO₂ (0.9 kPa, IQR 0.3–5.4), p=.008)) and a significant decrease following declamping (−0.7 kPa, IQR −2.6; −0.2), p=.011)). Conclusion: Transcutaneous monitoring of oxygen and carbon dioxide is a feasible method for detection of extreme changes in tissue perfusion during arterial clamping and declamping, and its use for improving patient outcomes should be explored. Clinical Trials identifier: NCT04040478. Registered on July 31, 2019.