OBJECTIVE: Fluid overload has been independently associated with increased morbidity and mortality in pediatric patients with renal failure, acute lung injury, and sepsis. Pediatric patients who undergo cardiopulmonary bypass are at risk for poor cardiac, pulmonary, and renal outcomes. They are also at risk of fluid overload from cardiopulmonary bypass, which stimulates inflammation, release of antidiuretic hormone, and capillary leak. This study tested the hypothesis that patients with fluid overload in the early postcardiopulmonary bypass period have worse outcomes than those without fluid overload. We also examined the timing of the association between postcardiopulmonary bypass acute kidney injury and fluid overload. DESIGN, SETTING, AND PATIENTS: Secondary analysis of a prospective observational study of 98 pediatric patients after cardiopulmonary bypass at a tertiary care, academic, PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Early postoperative fluid overload, defined as a fluid balance 5% above body weight by the end of postoperative day 1, occurred in 30 patients (31%). Patients with early fluid overload spent 3.5 days longer in the hospital, spent 2 more days on inotropes, and were more likely to require prolonged mechanical ventilation than those without early fluid overload (all p < 0.001). Fluid overload was associated with the development of acute kidney injury and more often preceded it than followed it. Conversely, acute kidney injury was not associated with more fluid accumulation. Patients with fluid overload were administered higher fluid volume over the study period, 395.4 +/- 150 mL/kg vs. 193.2 +/- 109.1 mL/kg (p < 0.001), and had poor urinary response to diuretics. Cumulative fluid administered was an excellent predictor of pediatric-modified Risk, Injury, Failure, Loss, and End-stage "Failure" (area under the receiver-operating characteristic curve, 0.963; 95% CI, 0.916-1.000; p = 0.002). CONCLUSIONS: Early postoperative fluid overload is independently associated with worse outcomes in pediatric cardiac surgery patients who are 2 weeks to 18 years old. Patients with fluid overload have higher rates of postcardiopulmonary bypass acute kidney injury, and the occurrence of fluid overload precedes acute kidney injury. However, acute kidney injury is not consistently associated with fluid overload.