BACKGROUND: The primary aim of this study was to compare the effects of a small-dose infusion of 2 antioxidant agents, ketamine and lidocaine, on ischemia-reperfusion injury (IRI) in patients undergoing elective lower limb surgery. Ischemia-modified albumin (IMA), lactate, and blood gas levels were all measured and assessed. METHODS: A total of 100 patients who underwent lower extremity surgery were randomized into 3 groups. After spinal anesthesia, the ketamine group (Group K, n=33) was given a ketamine infusion, a lidocaine infusion was administered to the lidocaine group (Group L, n=33), and in the control group (Group C), 0.9% a sodium chloride infusion was performed. Blood samples were obtained for IMA analysis before anesthetic administration (baseline), at 30 minutes of tourniquet inflation (ischemia), and 15 minutes after tourniquet deflation (reperfusion). Arterial blood gas measurements were determined before anesthetic administration and 15 minutes after tourniquet deflation. RESULTS: The lactate and IMA levels at reperfusion were significantly lower in both the ketamine group and the lidocaine group when compared with the control group. CONCLUSION: The administration of both ketamine and lidocaine infusions significantly decreased skeletal muscle IRI-related high lactate and IMA levels. These results suggest the possibility of the clinical application of ketamine or lidocaine infusions in cases of skeletal muscle-related IRI.