Objectives Low early-life leptin concentrations may promote faster weight gain in infancy. We aimed to examine the associations between cord blood leptin concentrations and changes in weight and body composition during infancy. Design and methods Serum leptin was measured at 15 weeks gestation, in umbilical cord blood collected at delivery and at 2 years in 334 children from the Cork Baseline Birth Cohort Study. Body composition was measured at 2 days and 2 months using air displacement plethysmography. Conditional change in weight standard deviation scores over a number of age intervals in the first 2 years and conditional change in fat mass index (FMI) and fat-free mass index (FFMI) (kg/(length)m²) between birth and 2 months were calculated and associations with cord blood leptin were examined using linear regression. Results At birth, cord blood leptin was positively correlated with FMI (r = 0.48, P < 0.001) and showed a weaker correlation with FFMI (r = 0.12, P = 0.05). After adjustment for confounders, higher cord blood leptin (per ng/mL) was associated with slower conditional weight gain between birth and 2 months (β (95% CI): −0.024 (−0.035, −0.013), P < 0.001) but not over subsequent age intervals. Cord blood leptin was also inversely associated with conditional change in FMI (−0.021 (−0.034, −0.007, P = 0.003) but not FFMI between birth and 2 months. Conclusions These are the first data to show that associations between higher cord blood leptin and slower weight gain during infancy are driven by lower increases in adiposity, at least in early infancy.