Carbon dioxide levels can affect inflammation and cerebral regional oxygen saturation (rScO2), a pathophysiological indicator of early postoperative cognitive dysfunction (POCD). To compare the cerebral rScO2 and postoperative inflammation based on patient end-tidal carbon dioxide (PET CO2) levels in elderly patients undergoing laparoscopic radical gastrectomy. Ninety patients were randomly divided into three groups according to PET CO2 level: group L (low PET CO2, 36-40 mmHg), group C (control PET CO2, 41-45 mmHg) and group H (high PET CO2, 46-50 mmHg). Eighty-four patients (age, range: 60-80 years) scheduled to undergo radical laparoscopic gastrectomy were included in the final analysis. The indicated PET CO2 was maintained for patients in each group. Their intraoperative cerebral rScO2 was recorded at indicated timepoints (T0-T6) from arrival at the operating room to post-extubation. The Montreal Cognitive Assessment Test (MoCA) and changes in serum concentrations of inflammatory cytokines were measured at 1 h, 1d and 7 d after surgery. The cerebral rScO2 at T3 (1 h post-skin incision)-T5 (completion of skin sutures) was significantly higher in group H than in group L, while the MoCA score was not significantly different between group H and L (p > 0.05). At 1 h, 1 d and 7 d after surgery, the concentrations of inflammatory cytokines, including interleukin 6 (IL-6) and S100ß, were significantly higher in group L than in group H (p < 0.05). At 1 h and 7 d after surgery, the inflammatory cytokines were significantly higher in group C than in group H. Our findings suggest that higher PET CO2 levels increased cerebral rScO2 and reduced the serum concentrations of IL-6 and S100ß but may not affect the MoCA score in elderly patients after radical laparoscopic gastrectomy. [ABSTRACT FROM AUTHOR]