Background: Cardiopulmonary bypass (CPB) is well known to be associated with a complex physiological response that is clinically manifested as a systemic inflammatory response syndrome. The aim of the study is to compare between the effect of morphine and fentanyl as part of a balanced anesthetic technique on the inflammatory reaction that occurs in cardiac valve replacement surgeries after CPB. Material and methods: Thirty patients undergoing cardiac surgery with cardiopulmonary bypass were randomized to receive either morphine or fentanyl as part of a standardized opioid-isoflurane anesthetic; Group 1 (15 patients received morphine, IV. Group 2 (15 patients received fentanyl. Hemodynamic data were recorded. Serum concentrations of interleukin [(IL)-6 and IL-10] and [(CD 11b, CD 11c, and CD 18] were measured. Results: There was a significant decrease in Heart Rate (HR) and Mean arterial pressure (MAP) in morphine group compared to fentanyl group. However, there were no significant differences between both groups in central venous pressure (CVP) and the incidence of intra operative arrhythmias. Serum levels of IL-6 and IL-8 concentrations increased in all patients after CPB. The increase in serum IL-6 levels was significantly attenuated in the morphine group compared to the fentanyl group at 3 and 24 hrs post CPB (P<0.05). The increase in IL-6 and IL-10 concentrations was significantly attenuated in morphine group compared to the fentanyl group at 4hrs and 24hrs post-CPB (P<0.05). The reduction in adhesion molecules expression (CD 11b, CD 11c and CD 18) were significantly more in the morphine group than in the fentanyl group at 4 hrs and 24 hrs post-CPB (P<0.05). Conclusion: There were perturbations in the release of circulating cytokines, adhesions molecules and postoperative hyperthermia which attenuated by the use of morphine. J o u rn al of A n e s th es ia & C li n ic a l Resea rc h