A relationship between the inflammatory response to cardiopulmonary bypass (CPB) and fever after coronary artery bypass graft surgery (CABG) is assumed, but has not been studied. Therefore, we sought to assess the temporal pattern of cytokines' elevation and its association with post-CABG fever. In 355 primary elective CABG patients, serum cytokines (TNF-alpha, IL-1ra, IL-1beta, IL-6, and IL-8) were measured before surgery, at cessation of CPB and 2.5, 4.5, 24, and 48 h post-CPB. Fever was defined as a temperature >38 degrees C. TNF-alpha, IL-1beta and IL-8 peaked within the first 2.5 h after bypass, returning to near normal levels by 24h and increasing again by 48 h. IL-6 peaked early after bypass and remained elevated at 48 h. IL-1ra was elevated early, before returning to baseline by 24 h. Postoperative fever developed in 27% of patients. Increased IL-6 levels and male gender were significant predictors of fever (C-index=0.68; p=0.0003). No other cytokine showed a significant association with fever development. Of note is the previously undescribed bimodal pattern of cytokines' secretion after CABG. The association of fever with IL-6 levels suggests inflammatory mediation.