Objective: The purpose of this study was to investigate the impact of varying dosages of S-ketamine on perioperative immune-inflammatory responses in patients undergoing modified radical mastectomy (MRM). Methods: This is a prospective, randomized, controlled trial. A total of 136 patients with American Society of Anesthesiologists status I/II scheduled for MRM were enrolled and randomly assigned into groups to receive control (C), or one of three different doses (0.25 [L-Sk], 0.5 [M-Sk], or 0.75 [H-Sk] mg/kg) of S-ketamine. Primary outcome was the cellular immune function and inflammatory factors before anesthesia, at the end (T1) and 24 h (T2) after surgery. Secondary outcomes included the Visual Analogue Scale (VAS) score, opioid consumption, rate of remedial analgesia, adverse events. Results: The percentage and absolute counts of CD3+ and CD4+ cells in group L-Sk, M-Sk and H-Sk were higher than group C both at T1 and T2, moreover, pairwise comparison revealed the percentage in group H-Sk were higher compared to L-Sk and M-Sk groups, (p — Read on www.frontiersin.org/articles/10.3389/fphar.2023.1128924/full