Objectives Evaluate the association of postoperative day (POD) 2 weight-based fluid balance (FB-W) > 10% with outcomes after neonatal cardiac surgery. Methods Retrospective cohort study of 22 hospitals in the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) registry from September 2015 to January 2018. Of 2240 eligible patients, 997 neonates (cardiopulmonary bypass (CPB) n  = 658, non-CPB n  = 339) were weighed on POD2 and included. Results Forty-five percent ( n  = 444) of patients had FB-W > 10%. Patients with POD2 FB-W > 10% had higher acuity of illness and worse outcomes. Hospital mortality was 2.8% ( n  = 28) and not independently associated with POD2 FB-W > 10% ( OR 1.04; 95% CI 0.29–3.68). POD2 FB-W > 10% was associated with all utilization outcomes, including duration of mechanical ventilation (multiplicative rate of 1.19; 95% CI 1.04–1.36), respiratory support (1.28; 95% CI 1.07–1.54), inotropic support (1.38; 95% CI 1.10–1.73), and postoperative hospital length of stay (LOS 1.15; 95% CI 1.03–1.27). In secondary analyses, POD2 FB-W as a continuous variable demonstrated association with prolonged durations of mechanical ventilation ( OR 1.04; 95% CI 1.02–1.06, respiratory support (1.03; 95% CI 1.01–1.05), inotropic support (1.03; 95% CI 1.00–1.05), and postoperative hospital LOS (1.02; 95% CI 1.00–1.04). POD2 intake–output based fluid balance (FB-IO) was not associated with any outcome. Conclusions POD2 weight-based fluid balance > 10% occurs frequently after neonatal cardiac surgery and is associated with longer cardiorespiratory support and postoperative hospital LOS. However, POD2 FB-IO was not associated with clinical outcomes. Mitigating early postoperative fluid accumulation may improve outcomes but requires safely weighing neonates in the early postoperative period. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information