Pediatric cardiac surgery with cardiopulmonary bypass (CPB) induces a complex inflammatory response that may cause multiorgan dysfunction. The objective of this study was to measure postoperative cytokine production and correlate the magnitude of this response with intraoperative variables and postoperative outcomes. Serum samples from 20 children (median age, 15 months) undergoing cardiac surgery with CPB were obtained preoperatively and on postoperative days (POD) 1-3. Serum levels of interleukin (IL)-6, IL-8, and IL-10 increased significantly on POD 1 (p < 0.01) vs pre-op values to 271 ± 68, 44 ± 9, 7.5 ± 0.8 pg/ml, respectively, whereas serum IL-1β, IL-12, and tumor neurosis factor -α were not significantly changed. The serum IL-6 and IL-8 levels correlated positively (p < 0.01) with the degree of postoperative medical intervention as measured by the Therapeutic Interventional Scoring System and indicated a greater need for inotropic support (p = 0.057). A negative correlation (p < 0.01) between IL-6, IL-8, and mixed venous oxygen saturation suggested compromised cardiopulmonary function. Patients with single ventricle anatomy had the highest levels of IL-6 and IL-8 (629 ± 131 and 70 ± 17 pg/ml, respectively), with a mean CPB time of 106 ± 23 minutes. Thus, the proinflammatory response after surgery with CPB was associated with postoperative morbidity with increased need for medical intervention.