The contact of blood with the artificial extracorporeal circuit causes a systemic inflammatory response due to blood activation. In this study, we compared two different paediatric membrane oxygenators used for extracorporeal circulation: a hollow fibre membrane oxygenator (Dideco Masterflo D-701, n = 10), and a flat sheet silicone membrane oxygenator (Avecor Kolobow 800-2A, n = 10). Blood compatibility was indicated by measuring complement activation as well as leukocyte and platelet activation. In patients perfused with a flat sheet membrane oxygenator, concentrations of complement split products C3a were significantly increased 30 minutes after the start of bypass (p < 0.01), whereas only a mild increase of C3a was found in patients perfused with a hollow fibre membrane oxygenator. Leukocyte and platelet counts dropped uniformly in both groups after the start of bypass mainly due to hemodilution. Activation of leukocytes and platelets identified by both plasma beta-glucuronidase and beta-thromboglobulin was similar in both groups. Infants perfused with a flat sheet membrane oxygenator received significantly more donor blood than those perfused with a hollow fibre oxygenator (p < 0.05). These results indicate that when used during paediatric cardiopulmonary bypass, a flat sheet membrane oxygenator has a higher complement activity than a hollow fibre membrane oxygenator, which is probably due to the relatively larger blood-surface contacting area of the oxygenator.