Background: Systemic inflammatory responseplays pivotal roles in the pathogenesis of organ dysfunction after cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to investigate whether remifentanil has the effects on the systemic inflammatory responseinduced by cardiac surgerywith CPB. Methods: Sixty adult patients undergoing cardiac surgery with CPB were randomly assigned to two groups: a remifentanil (n = 30) and a fentanyl group (n = 30). The plasma levels of IL-6, IL-8 and malondialdehyde (MDA) were measured at preinduction (T1), just before aortic clamping (T2), just before aortic declamping (T3), 5 (T4), 30 (T5), and 60 (T6) min after aortic declamping. Hemodynamic variables serially recorded at that same times. Myocardial cell damage as assessed by plasma level of creatine kinase-MB (CK-MB) andtroponin T were measured before and 24 hr after surgery. Results: The levels of IL-6, IL-8 and MDAsignificantly increased from just before aortic declampingin both groups. In the remifentanil group, all of those were significantly lower compared to the fentanyl group from just before aortic declamping(P < 0.05). The level of CK-MB andtroponin T significantly increased at 24 hr after surgery than preoperative baseline in both groups. In the remifentanil group, both were significantly lower than fentanyl group at 24 hr after surgery. Conclusion: Remifentanil attenuatessystemic inflammatory responsemore effectively than fentanyl in cardiac surgery with CPB. The mechanism of its effects is likely to be through proinflammatory cytokines (including IL-6, IL-8) and oxidative stress mediator (MDA).