Introduction: In the present study, changes in hemodynamic parameters and cerebral oxygen saturation (rSO2) associated with 10 cm H2O PEEP application were investigated, which is assumed beneficial for the respiratory functions and oxygenation during laparoscopic cholecystectomy (LC) applied at 30° head-up left side position. Data gathered via two devices, namely INVOS and FORESIGHT, were compared. Methods: After both the ethics committee approval from the hospital and patients’ written consents were obtained, patients undergoing elective laparoscopic surgery (only ASA I–II) were randomly divided into two groups (Clinical trials protocol NCT02071550). Sensors of INVOS and FORESIGHT devices were placed on the right side at the forehead region. In total, 11 evaluation periods were formed, namely pre-induction (1st period), post-induction (2nd period), abdominal insufflation outset (3rd period), post-insufflation at 5-min intervals (4th, 5th, 6th, 7th, and 8th period), at the end of insufflation (9th period), at the end of operation (10th period), and at the end of anesthesia (11th period). While one of the groups did not receive PEEP (ZEEP group), the other group received 10 cm H2O along with abdominal insufflation (PEEP group). Demographic data, hemodynamic values, and rSO2 values were recorded for both groups at all 11 periods. Results: A total of 44 patients in two groups, each group containing 22 individuals, were included in the study. Systolic, diastolic, and mean arterial pressures, etCO2 and SO2 values, and demographic data were found to be similar in both groups. Heart rate was observed to be higher in the PEEP group starting with the PEEP administration. INVOS rSO2 values were found similar in both groups. However, FORESIGHT rSO2 values were found to be higher in the PEEP group compared to the ZEEP group. No patient had cerebral desaturation in both groups throughout the study. Discussion: Application of PEEP with 10 cm H2O during abdominal insufflation could increase the rSO2 value and heart rate in patients undergoing laparoscopic cholecystectomy. However, all changes observed were within normal limits. FORESIGHT device yielded more compatible results with hemodynamic data compared to INVOS.