Objective To investigate the effect of dexmedetomidine combined with sevoflurane on lung injury in the patients undergoing cardiopulmonary bypass. Methods A total of 80 patients scheduled for heart valve replacement under cardiopulmonary bypass were recruited and randomly divided into 4 groups (n=20):dexmedetomidine group (D group), sevoflurane group (S group), dexmedetomidine combined with sevoflurane group (DS group) and control group. For the patients of groups D and DS, dexmedetomidine were continuously pumped into vein with the loading dose of 0.8μg/kg 10 min before introduction of general anesthesia, and then the speed was adjusted to 0.6μg/(kg·h) to the end of surgery. For those from groups S and DS, 2% sevoflurane was inhaled for 15min before and after the ascending aorta was blocked, and also before and after the ascending aorta was opened. Oxygenation index (OI), alveolar-arterial oxygen partial pressure difference [P(A-a)O₂], static compliance (Cst), and plasma levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (sICAM-1) were recorded and measured before anesthesia induction (T1), immediately after cardiopulmonary bypass (T2), after surgery (T3), and 1 d after surgery (T4). SPSS statistics 21.0 was used to perform the statistical analysis. Results The plasma levels of TNF-α, IL-8 and sICAM-1 in control group were the highest when compared with those in the other 3 groups at T2-T4 (P<0.05), and the levels was significantly lower in DS group than those of D group and S group at T2-T4 (P<0.05). At the time period, the P(A-a)O₂ was significantly higher while the OI and Cst were obviously lower in control group than in the other 3 groups (P<0.05). And the P(A-a)O₂ of DS group was significantly lower than that of the D group and S group (P<0.05), and OI and Cst were notably higher than those of the D group and S group (P<0.05). Conclusion Sevoflurane combined with dexmedetomidine can alleviate lung injury in the patients undergoing cardiopulmonary bypass, and the effect is better than the combined anesthesia of sevoflurane and dexmedetomidine alone.