Apolipoprotein E (apoE) may play a critical role in modulating the response to neurological injury after cardiopulmonary bypass (CPB) in children. Plasma samples were collected from 38 pediatric patients. Half of the patients received nonpulsatile flow and the other half underwent pulsatile flow during CPB. Plasma samples were collected at three time points: at baseline prior to incision (T1), 1h after CPB (T2), and 24h after CPB (T3). The study included 38 pediatric patients undergoing heart surgery (mean age 2.5 +/- 2.1 years). Baseline apoE levels were low (<30g/mL) in 21 patients (55%). ApoE levels were significantly decreased at 1h after CPB compared with baseline (22 +/- 14vs. 34 +/- 18g/mL, P=0.001). At 24h after CPB, apoE levels were significantly increased compared with baseline (47 +/- 25 vs. 34 +/- 18g/mL, P=0.002). Pulsatile mode was associated with lower apoE levels at 24h after CPB compared with nonpulsatile mode (38 +/- 14 vs. 57 +/- 29g/mL, P=0.018). ApoE levels correlated negatively with pump time (r=-0.525, P=0.021) and cross-clamp time (r=-0.464, P=0.045) at 24h following CPB for the nonpulsatile group but not for the pulsatile group. In this cohort of young children with congenital heart disease, baseline apoE levels were low in the majority of patients prior to surgery. ApoE levels decreased further at 1h after CPB, and then significantly increased by 24h. The mode of perfusion and the duration of pump time and clamp time influence the apoE levels after CPB. An improved understanding of these mechanisms may translate into the development of new techniques to improve the clinical outcomes after pediatric CPB.