Lactate clearance is a key marker of oxygen delivery after neonatal cardiac surgery. While higher hematocrit (HCT) is often targeted to optimize oxygen delivery, its relationship with postoperative lactate clearance remains unclear. We hypothesized that supraphysiologic initial HCT may decrease lactate clearance. To assess whether higher initial postoperative HCT is associated with delayed lactate clearance. We performed a retrospective cohort study of 201 neonates requiring CPB. Clinical data were extracted from the EHR using standardized PC4 and STS definitions. The primary predictor was initial HCT analyzed as a continuous variable. Outcomes were lactate at 1, 6, 12, and 24 h and lactate trajectories over 24 h. Multivariable linear regression adjusted for demographics, surgical complexity, and CPB time. Linear mixed-effects models assessed longitudinal lactate trajectories. Initial postoperative HCT (median = 51, IQR = 47–56) was not associated with post-operative lactate after adjustment. However, each 10% increase in HCT was associated with higher lactate at 1 h (adjusted β = 0.40 mmol/L, 95% CI 0.03–0.80; p = 0.03). In mixed-effects models, HCT was not associated with lactate trajectories in the primary model but was associated after adjustment for time-varying variables (β = 0.29, 95% CI 0.03–0.55; p = 0.03). Higher initial postoperative HCT was not associated with lactate, but it was associated with lactate trajectories when adjusting for time-varying variables. Further studies are needed to define optimal transfusion strategies in this population, and caution may be indicated when increasing HCT to supra-physiological levels.