Background: Cardiac valve replacement (CVR) is currently the main surgical treatment for patients with valvular heart diseases (VHD). Postoperative cognitive dysfunction (POCD) is one of the most serious complications of cardiac surgery.. Permissive hypercapnia (PHC), an important lung-protective ventilation strategy, has protective effects on vital organs, including the heart, lungs, and central nervous system (CNS). The main objective of this study is to assess the effect of the PHC ventilation strategy on rSO 2 and postoperative cognitive function in patients undergoing CVR.Methods: A total of 66 patients undergoing CVR were included and randomly divided into the PHC ventilation group (Group H, n=33) and conventional ventilation group (Group C, n=33). Patients of both groups were subjected to conventional ventilation before cardiopulmonary bypass (CPB). patients in Group H were subjected to the PHC ventilation strategy to keep the partial pressure of carbon dioxide (PaCO 2 ) at 46-60 mmHg.Results: (I) Group H had a lower HR at T0 and T1 (P<0.05) and higher CO at T3 and T4 (P<0.05) than Group C. (II) Group H had higher rSO 2 at T4 (P<0.05), lower pH and lactate (Lac) at T4 (P<0.05), higher PaCO 2 at T3 and T4 (P<0.05), and lower PaO 2 at T3 and T4 (P<0.05). (III) Compared to 1 d before surgery, the MMSE scores of both groups were lower 24 h after surgery (P<0.05).Conclusions: PHC can increase the rSO 2 of patients undergoing CVR, increase cerebral blood flow, improve the cerebral oxygen supply/consumption balance, and play a protective role in the brain. It has no significant impact on the incidence of POCD.