During cerebral ischemia, the quantitative Electroencephalogram (EEG) Alpha: Delta Ratio (ADR) decreases, and the asymmetry percentage increases. The utility of analyzing these metrics during neonatal Antegrade Cerebral Perfusion (ACP) or Deep Hypothermic Circulatory Arrest (DHCA), and whether significant EEG changes precede neurologic injury after pediatric cardiac surgery, remains unknown. Neonates requiring DHCA or ACP with intraoperative EEG monitoring were retrospectively reviewed, and the left and right anterior, posterior, and hemispheric ADRs and asymmetry percentages were measured every 5 min throughout cardiopulmonary bypass. A paired right versus left cerebral ADR difference of > 25% or an asymmetry percentage of > 50% was considered significant for ischemia, and the cumulative duration of time was calculated. Neurologic injury was defined as postoperative stroke or seizure. Among 86 neonates, 14 (16.2%) underwent a period of DHCA and 72 (83.8%) ACP. The ADR remained similar during ACP but decreased significantly during DHCA. The asymmetry percentage remained similar during DHCA but increased significantly during ACP. From the 11 neonates (ACP = 7, DHCA = 4) that developed neurologic injury, although there were no significant differences in the duration of significant asymmetry, neonates with neurologic injury had longer anterior right vs. left ADR differences > 25% (25 [IQR 0–65] vs. 5 [IQR 0–15] minutes, p < 0.001), which was confirmed using multivariate analysis (OR 1.044; 95% CI 1.010–1.080; p = 0.012). The ADR decreased significantly during DHCA, the asymmetry percentage increased during ACP, and a prolonged anterior right vs. left ADR difference preceded neurologic injury.