Infants who are unable to maintain oral feeding can be nourished continuously by orogastric tube. We have previously shown in neonatal pigs that a leucine pulse administered during continuous feeding enhanced protein synthesis in skeletal muscle compared to continuous feeding alone for a 24 h period. Twenty‐three piglets (7‐d‐old) were fed continuously a milk replacement formula via orogastric tube for 21 d with an additional parenteral infusion of either leucine (800 μmol•kg−1•h−1, LEU) or alanine (ALA) for 1 h every 4 h. At 21 d, the body weight was higher and the weight gain greater in LEU than in ALA pigs. The lean gain, determined by dual‐energy X‐ray absorptiometry (DEXA), was higher and the fat gain lower in the LEU than ALA group. Longissimus dorsi (LD), gastrocnemius and soleus muscle and kidney weights were heavier in LEU than ALA with no effect of treatment on liver, small intestine and heart weights. Fractional protein synthesis rate and formation of the active eukaryotic initiation factor (eIF) eIF4E•eIF4G complex in LD were greater in the LEU than ALA group. In conclusion, administration of a leucine pulse during 21 d of continuous feeding decreases fat gain and increases lean gain by stimulating the translation initiation pathway leading to protein synthesis in skeletal muscle in neonates. (NIH AR444474 and USDA/ARS 6250–51000‐055)Grant Funding Source: NIH AR444474 and USDA/ARS 6250–51000‐055