Abstract: BACKGROUND: This study prospectively investigated the levels of energy metabolism hormones in very preterm neonates to identify their change over time and association with intake of maternal milk as well as weight gain velocity. METHODS: We measured and compared the leptin, adiponectin, ghrelin, and insulin-like growth factor I (IGF-1) levels in the urine of 70 very preterm neonates, before the initiation of any enteral feeding (baseline level) and twice within 14 days on full enteral feeding (FEF). Regression models identified the role of intake of maternal milk on the levels of the tested energy metabolism hormones in the enteral-fed infants. We also analyzed the adequacy of the weight gain velocity defined by the fetal-infant growth reference (FIGR). Additionally, we collected and analyzed the infants’ clinical and feeding characteristics during the birth hospitalization. RESULTS: The preterm infants’ baseline levels of the energy metabolism hormones significantly predicted their increase at the end of two weeks of observation on FEF. The leptin level was associated with increased intake of maternal milk, whereas the feeding volume was associated with increased ghrelin and IGF-1, and decreased leptin and adiponectin. Infants with comparable FIGR had higher leptin levels than those with inadequate weight gain velocity. CONCLUSION: Early postnatal levels of leptin, adiponectin, ghrelin, and IGF-1 predicted the increase of these hormones in the fully enteral fed very preterm neonates. Moreover, greater intake of maternal milk by the study infants contributed to an increased leptin-associated weight gain velocity.