In this paper, we have carried out an experimental study to investigate the effects of different anesthetics on perioperative organ protection and postoperative cognitive function in patients undergoing cardiac valve replacement with cardiopulmonary bypass. To realize this idea, a total of 90 patients with single valve replacement under general anesthesia and hypothermic cardiopulmonary bypass from January 2020 to October 2021 were enrolled. These patients were assigned into three groups, with 30 cases in each group by the digital table method. Group A was anesthetized with sufentanil combined with dexmedetomidine. Group B was anesthetized with sufentanil combined with etomidate. Group C was anesthetized with sufentanil combined with propofol. Perioperative organ protection and postoperative cognitive function of the three groups were compared. At T0 time point, there was no significant difference in blood WBC, blood N, and CRP among groups A, B, and C (
P
> 0.05); At T4 and T5 time points, the indexes of blood WBC, blood N, and CRP in groups A, B, and C were higher compared to the T0 time point. At T4 and T5 time points, the indexes of blood WBC, blood N, and CRP in group A were significantly lower compared to group B and group C. Before treatment, there was no significant difference in ALT and AST among groups A, B, and C (
P
> 0.05). After treatment, the indexes of ALT and AST in group A were significantly lower compared to group B and group C at T4 and T5 time points (
P
< 0.05). Before treatment, there was no significant difference in urea and creatinine among groups A, B, and C (
P
> 0.05). After treatment, the urea and creatinine indexes of group A were significantly lower compared to group B and group C at T4 and T5 time points (
P
< 0.05). Before treatment, there was no significant difference in CK-MB and CTnl among groups A, B, and C (
P
> 0.05); After treatment, the indexes of CK-MB and CTnl in group A were significantly lower compared to group B and group C at T4 and T5 time points (
P
< 0.05). Before treatment, there was no significant difference in MOCA scores among groups A, B, and C (
P
> 0.05). After treatment, the MOCA scores of group A were significantly higher compared to group B and group C at T5 and T6 time points (
P
< 0.05). Sufentanil combined with dexmedetomidine for heart valve replacement under cardiopulmonary bypass can reduce the dosage of anesthetics during the operation and have a certain perioperative protective effect on important organs such as the heart, lung, liver, and kidney, which may be related to reducing intraoperative hemodynamic fluctuations and inhibiting inflammatory stress response.