Long-term neurodevelopmental sequelae are commonly detectable in children after open-heart surgery with cardiopulmonary bypass (CPB). The objective of the study was to determine the neurodevelopmental outcome in these children in relation to postoperative inflammatory reaction. This is a prospective, observational study on children with congenital heart defects (n = 32) undergoing elective open-heart surgery in a tertiary pediatric cardiac center. Neurodevelopmental outcome was assessed in the median 6 months after CPB. Neurological examination was done in all children before the operation and, additionally, complete neurodevelopmental status was assessed preoperatively in 14 children. Three hours after the end of CPB, plasma concentrations of interleukin (IL)-6 and IL-8 were strongly elevated (p < 0.001). Moreover, there was a rise of neutrophils and C-reactive protein at 24 h postoperatively (p < 0.001). Intellectual performance after surgery was correlated with preoperative performance, r ( S ) = 0.83, p < 0.001 (mean IQ scores after CPB = 90.4 +/- 18.4 and before CPB = 87.5 +/- 14.5, p = 0.20). Multiple regression analysis demonstrated that preoperative IQ scores accounted for 83.8% of the variance of postoperative IQ scores (p < 0.0001). Inflammatory variables were not significant predictors of postoperative IQ scores. The frequency of neuromotor abnormalities at 6 months after CPB was influenced by the presence of a cyanotic heart defect, duration of CPB and aortic clamp time, and plasma levels of IL-6 shortly after CPB (R (2) = 67.8%, p = 0.002). In conclusion, in the examined population, preexisting neurodevelopmental impairment is frequent and predicts postoperative outcome. The high frequency of postoperative neuromotor disabilities seems to be associated with the type of congenital heart defect but also with the procedure and possible complications of CPB.