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Background Early adequate fluid infusion could prevent organ hypoperfusion after surgery. However,exces-sive fluid expansion after pediatric cardiac surgery adversely influences multiple organ systems. This retrospec-tive,observational study aimedto determine the relationship between the first 24 hours postoperative positive flu-id balance and mortality and morbidity in neonates undergoing cardiac surgery. Methods In total,256 neonates who had undergone cardiovascular surgery were enrolled. The baseline characteristics,fluid input,output,and clinical outcomes were obtained. Fluid balance was calculated as(total fluid in total fluid out). Cox proportional-hazards regressions were used to analyze the relationship between early positive fluid balance and postoperative mortality. Results No difference was observed between the positive fluid balance group and negative fluid bal-ance group in terms of age,weight,height,RACHS-1 score,cardiopulmonary bypass time,and aortic cross-clamp time. Positive fluid balance group patients were more likely to have a higher rate of male(P=0.01),more peritoneal drainage after surgery(P=0.015),higher maximum vasoactive-inotropicscore(P<0.001)than those with negative fluid balance. There was no difference in the duration of mechanical ventilation and hospital length of stay after surgery between two groups(P=0.296 and 0.38,respectively).Predictors of in-hospital mortality from multivariate analyses were cardiopulmonary bypass time(HR 1.01,95％CI 1.002-1.021,P=0.013),chest drainage(HR 1.01,95％CI 1.000-1.011,P=0.045),and positive fluid balance(HR 7.85,95％CI 1.395-44.159,P=0.019). Conclusions Early postoperative positive fluid balance is associated with higher mortality in neonates following cardiopulmonary bypass cardiac surgery. However,postoperative positive fluid balance is not associat-ed with increased duration of mechanical ventilation and hospital length of stay.