© 2019 Cambridge University Press. Hypoalbuminemia is associated with morbidity and mortality in critically ill children. In this multi-centre retrospective study, we aimed to determine normative values of serum albumin in neonates and infants with congenital heart disease, evaluate perioperative changes in albumin levels, and determine if low serum albumin influences post-operative outcomes. Consecutive eligible neonates and infants who underwent cardiac surgery with cardiopulmonary bypass at one of three medical centres, January 2012-August 2013, were included. Data on serum albumin levels from five data points (pre-operative, 0-24, 24-48, 48-72, 72 hours post-operative) were collected. Median pre-operative serum albumin level was 2.5 g/dl (IQR, 2.1-2.8) in neonates versus 4 g/dl (IQR, 3.5-4.4) in infants. Hypoalbuminemia was defined as <25th percentile of these values. A total of 203 patients (126 neonates, 77 infants) were included in the study. Post-operative hypoalbuminemia developed in 12% of neonates and 20% of infants; 97% occurred in the first 48 hours. In multivariable analysis, perioperative hypoalbuminemia was not independently associated with any post-operative morbidity. However, when analysed as a continuous variable, lower serum albumin levels were associated with increased post-operative morbidity. Pre-operative low serum albumin level was independently associated with increased odds of post-operative hypoalbuminemia (OR, 3.67; 95% CI, 1.01-13.29) and prolonged length of hospital stay (RR, 1.40; 95% CI, 1.08-1.82). Lower 0-24-hour post-operative serum albumin level was independently associated with an increased duration of mechanical ventilation (RR, 1.35; 95% CI, 1.12-1.64). Future studies should further assess hypoalbuminemia in this population, with emphasis on evaluating clinically meaningful cut-offs and possibly the use of serum albumin levels in perioperative risk stratification models.