Objective: To study the effect of prenatal and postnatal glucocorticoids use on serum leptin and weight gain in sick preterm infants and its correlation with calorie intake. Methods: Serum leptin was measured in 24 neonates at day 1 (cord), 14 and 28 by radioimmunoassay. Total caloric intake (enteral and parenteral) and weight were measured on days 14 and 28 of life. Results: Mean birth weight and gestational age of study infants were 864 ± 273 g (mean ± SD) (range 520-1755 g), and 26.6 ± 2.4 weeks (23-32 weeks) respectively. Cord blood leptin was greater in infants whose mothers received antenatal steroids (1.98 ± 1.05 ng/ml vs 0.94 ± 0.39 ng/ml, p=0.004). Serum leptin increased postnatally from 1.52 ± 1.0 ng/ml at birth to 2.2 ± 1.3 ng/ml on day 28 of life (p=0.03). Mean serum leptin had an inverse exponential relationship with postnatal weight gain by day 28 of life (R2=0.56). Total caloric intake on days 14 and 28 of life did not correlate with postnatal weight gain. Conclusions: Increased serum concentration of leptin following glucocorticoids may be associated with poor weight gain in sick preterm infants.