Infants unable to maintain oral feeding can be nourished by orogastric tube. We have shown that orogastric continuous feeding restricts muscle protein synthesis compared to intermittent bolus feeding in neonatal pigs. To determine whether leucine infusion can be used to enhance protein synthesis during continuous feeding, neonatal piglets received the same amount of formula enterally by orogastric tube for 25.25 h continuously (CON) with or without LEU or intermittently by bolus every 4 h (BOL). For the CON+LEU group, leucine pulses were administered parenterally (800 μmol • kg^-1 • h^-1) every 4 h. Insulin and glucose concentrations increased after the BOL meal and were unchanged in groups fed continuously. LEU infusion during CON feeding increased plasma leucine after the leucine pulse and decreased essential amino acids compared to CON feeding. Protein synthesis in longissimus dorsi (LD), gastrocnemius, and soleus muscles, but not liver or heart, were greater in CON+LEU and BOL than in the CON. BOL feeding increased protein synthesis in the small intestine. Muscle S6K1 and 4E-BP1 phosphorylation and active eIF4E•eIF4G complex formation were higher in CON+LEU and BOL than CON but AMPKα, eIF2α, and eEF2 phosphorylation were unchanged. LC3-II to total LC3 ratio was lower in CON+LEU and BOL compared to CON but there were no differences in atrogin-1 and MuRF-1 abundance and FoxO3 phosphorylation. In conclusion, administration of leucine pulses during continuous orogastric feeding in neonates increases muscle protein synthesis by stimulating translation initiation and may reduce protein degradation via the autophagy-lysosome, but not the ubiquitin-proteasome pathway.