Purpose: Although positive end-expiratory pressure (PEEP) is commonly used to improve respiratory mechanics and oxygenation during pneumoperitoneum (PP), the effect of PEEP on cerebral homeostasis during carbon dioxide PP remains uncertain. This study investigated the changes in regional cerebral oxygen saturation (rSO 2) associated with 0, 5, and 10 cm H 2 O PEEP during PP while undergoing laparoscopic cholecystectomy under sevoflurane anesthesia. Materials and Methods: In total, 105 patients between the ages of 18 to 60 years, scheduled to undergo laparoscopic cholecystectomy under general anesthesia, were studied. The patients were randomized, into 3 groups: Group I (n=35) with no external PEEP, group II (n=35) with external PEEP of 5 cm H 2 O, group III (n=35) with external PEEP of 10 cm H 2 O. Heart rate, mean blood pressure, oxygen saturation, and rSO 2 values were continuously recorded from awake status to tracheal extubation. Results: The measurements of hemodynamic parameters were statistically similar between 3 groups (P>0.05). rSO 2 values were statistically similar between 3 groups (P>0.05). Conclusions: We consider that both 5 and 10 cm H 2 O PEEP levels can be safely used during PP applied during laparoscopic surgery, without affecting hemodynamics, and without causing a decline in rSO 2.