The cytokine network and its association with complement activation during cardiac surgery with cardiopulmonary bypass (CPB) is complex. Extracorporeal membrane oxygenation (ECMO) differs from CPB in duration of days to weeks rather than hours. However, few studies have analyzed the levels of inflammatory mediators during ECMO treatment. Plasma samples from 22 patients [nine neonates, one infant, four children and eight adults (14 males and eight female)] who underwent ECMO treatment were collected prior to, during and after treatment, and analyzed for concentrations of inflammatory and anti-inflammatory cytokines and parameters of complement activation. Seven children were treated for cardiac and seven for pulmonary failure and, in the adult group, four were treated for cardiac and four for pulmonary failure. ECMO was performed with veno-arterial (VA) bypass in all children and five adults, and with veno-venous (VV) bypass in three adults. Fourteen patients survived (64%) and eight (36%) patients died during follow-up. A marked (approximately 99%) and rapid (i.e., within two days) decrease in IL-6 was seen in survivors. The non-survivors were characterized by persistently high IL-6 levels throughout the observation period (i.e., until death). C-reactive protein (CRP) levels showed a similar pattern as the IL-6, with higher levels in non-survivors throughout the observation period. However, in contrast to IL-6, the differences between survivors and non-survivors reached statistical significance, but only at the end of the observation period. It is possible that early measurements of IL-6 in ECMO patients could give prognostic information beyond that of CRP.