Extracorporeal circulation (ECC) is an essential tool for the execution of cardiac operations. However, ECC is also associated with undesirable side effects. These include the induction of a systemic inflammatory response associated with leukocyte activation and cytokine release as well as potentially life-threatening complications. The volatile anesthetic sevoflurane has been reported to exert anti-ischemic and anti-inflammatory effects. We therefore investigated whether sevoflurane modulates the ECC-triggered inflammatory response. Heparinized human blood was circulated for 90 min in a normothermic (37°C) ex vivo ECC circuit. An air-oxygen mixture was administered via an oxygenator in controls (n=5). Sevoflurane (2 vol.%) was added to the gas mixture in a second group (n=5). At baseline and after 30, 60 and 90 min of ECC, blood samples were taken. In each sample whole blood counts were determined. Expression of the activation-indicating Mac-1 receptor on granulocytes and monocytes as well as leukocyte-platelet aggregate formation was measured in flow cytometry. Levels of the granulocyte activation marker PMN-elastase and of the cytokines IL-1β, IL-8 and TNF-α were analyzed using ELISA. ECC induced significant increases in Mac-1 expression on granulocytes (p<0.001) and PMN-elastase release (p<0.001). Sevoflurane decreased granulocyte Mac-1 expression during ECC (p<0.05) and inhibited the ECC-induced PMN-elastase release (p<0.05). Sevoflurane had no effect on whole blood cell counts, leukocyte-platelet aggregate formation and cytokine release during ECC. Sevoflurane inhibits granulocyte activation during ex vivo ECC and therefore has the potential to decrease the ECC-triggered inflammatory response. This promising finding warrants further investigation under clinical conditions.