BACKGROUND Abdominal surgery is associated with a systemic inflammatory response which facilitates postoperative complications through immune imbalance and hypercatabolism. The aim of the study was to evaluate the effect of the combined perioperative lidocaine, magnesium, and amino acids on postoperative inflammation and pain. MATERIAL AND METHODS This prospective, randomized, double-blind study included 2 groups of patients undergoing abdominal surgery: Group 1 – receiving the aforementioned substances; and Group 2 – control (undergoing conventional general anesthesia). The following parameters were evaluated intraoperatively: arterial blood pressure, end-tidal CO₂ level, urine output, bispectral index, base excess, oxygen saturation, operating room temperature and body temperature (BT), opioid use, and surgery duration; and postoperatively: total leukocyte (WBC), neutrophil, lymphocyte and platelet count; fibrinogen, C-reactive protein (CRP), procalcitonin (PCT) and interleukin (IL)-6 levels; numeric rating scale (NRS) pain level, first flatus and bowel movement, and postoperative complications. The postoperative parameters were evaluated 2 h and 6 h postoperatively, as well as on postoperative days (POD) 1, 2, 3, and 5. RESULTS Group 1 showed lower counts of WBC, neutrophils, and lymphocytes and lower fibrinogen, CRP, PCT, IL-6, and BT in the first 5 POD, as well as NRS scores and time to first flatus/bowel movement. The groups did not differ significantly regarding postoperative complications. CONCLUSIONS The isolated effects of lidocaine, magnesium, and amino acids in surgery have been described previously. To the best of our knowledge, this is the first study to show the anti-inflammatory and analgesic effects of simultaneous use of these substances in abdominal surgery.