Abstract: Objective To investigate the relationship between the occurrence of post-operative cognitive dysfunction (POCD) after heart valve replacement (HVR) and the changes of regional brain tissue oxygen saturation (rSO2). Methods In this study, 82 patients with elective heart valve replacement were enrolled. After entering the operating room, cerebral oxygen saturation was monitored. The baseline value of rSO2（rSO2base）, the minimum value of rSO2 ( rSO2min) and the maximum percentage of decrease relative to the baseline (rSO2%max), and the area enclosed by threshold line below 20% of the baseline value and the curve ( AUT20%). The cognitive function was evaluated by the neuropsychological test methods 1 day before and 7 days after surgery. The patients were divided into POCD group and non-POCD group according to the evaluation results. The differences of rSO2 between the two groups were compared. Results There were 34 patients in the POCD group and 48 patients in the non-POCD group. The incidence of POCD was 41.5%. The rSO2%max and AUT 20% of the POCD group were higher than the non-POCD group（P＜0.05）. Conclusion Early cognitive dysfunction after heart valve replacement has a certain correlation with regional brain tissue oxygen saturation. Minimizing the exposure time of rSO2 below baseline by 20% may help reduce the incidence of POCD.