Maximizing growth during the neonatal period in preruminants can enhance long-term growth and productivity, increasing producer profits and input efficiency. Meeting the requirements for growth can be achieved through feeding singular amino acids, specifically leucine, to enhance protein synthesis in muscle tissues. In order to evaluate the impact of supplemental leucine in milk replacer fed to neonatal preruminants, three experiments were designed. Experiment 1 examined short-term effects of supplemental leucine administration on calf and organ growth, nutrient digestibility and nitrogen retention, serum amino acid and metabolite profiles, and regulators of protein synthesis. Experiment 2 determined long-term effects of supplemental leucine administration during the pre-weaning phase on pre- and post-weaning lamb growth, pre-weaning serum amino acid and metabolite profiles, feedlot performance, and carcass characteristics. Experiment 3 evaluated effects of supplemental leucine on the pancreatic enzymes α-amylase and trypsin, and the small intestinal carbohydrases maltase, isomaltase, glucoamylase, and lactase using tissue samples from experiments 1 and 2. Overall, supplemental leucine was able to affect animal productivity in the short- and long-term in a species-specific manner. In experiment 1, calf growth was unaffected by treatment; however, select tissue masses were affected by supplementation. Digestibility of milk replacer and nitrogen retention were also unaffected. Supplemental leucine was able to alter serum amino acid and metabolite profiles, but did not alter the activity of proteins involved in protein synthesis. In experiment 2, supplemental leucine increased pre-weaning lamb growth and average daily gain, but did not alter animal performance in the feedlot. Organ masses were unaffected, and lambs receiving supplemental leucine carried more fat in the carcass. In experiment 3, supplemental leucine had no effect on pancreatic enzyme activity, but had both a short- and long-term effect on small intestinal carbohydrase activities in both species, diminishing the activity of maltase and isomaltase in the jejunum. In calves, leucine also decreased lactase activity in the jejunum. These results suggest that leucine supplementation to milk replacer may affect short-term growth and development of neonatal preruminants, and does have a short- and long-term effects on intestinal carbohydrase activities, and future research should evaluate its effects on carbohydrate digestibility.