This study was conducted to determine the ability of a supplemental nucleotide mixture high in inosine 5'-monophosphate (5'IMP) to enhance pig growth and health after weaning. Pigs (n = 120 and 7.3 ± 0.1 kg) were allotted at weaning to phase 1 diets (3.3 Mcal ME/kg, 22.4% CP, and 1.34% standardize ileal digestible [SID] Lys) supplemented with 0.0, 0.2, 0.5, or 1.0 g/kg of a nucleotide additive. After 7 d, pigs were fed phase 2 diets (3.3 Mcal ME/kg, 21.3% CP, and 1.20% SID Lys) for 21 d with the same additive levels. Growth performance was measured, blood samples were collected for analysis of immune responses and oxidative stress, and fecal scoring was completed. During phase 1, ADG, ADFI, and G:F linearly increased (P < 0.05) as dietary nucleotides increased. During phase 2, ADFI increased linearly (P < 0.05). Over the entire 28-d trial, ADG and ADFI increased linearly (P < 0.05) as nucleotide content increased. Immune responses were not altered during phase 1. At the end of phase 2, IgA showed a quadratic effect (P < 0.05) with the lowest concentrations at 0.2 and 0.5 g/kg of the nucleotide additive whereas IgM changed cubically (P < 0.05) with the lowest concentration at 0.5 g/kg. The cytokine tumor necrosis factor-α tended to decrease linearly (P = 0.093) as nucleotide content increased whereas the marker for oxidative DNA damage, 8-hydroxy-deoxyguanosine, tended to have a quadratic effect (P = 0.064) with the lowest levels of damage in pigs fed 0.5 g/kg. On d 8 after changing from the phase 1 to phase 2 diets, fecal diarrhea scores tended to be lowest (P = 0.072) when pigs were fed 0.5 g/kg of the nucleotide additive. Overall, 1.0 g/kg of the nucleotide additive provided the most benefit to the growth performance of nursery pigs. However, 0.5 g/kg of the nucleotide additive reduced immune responses and oxidative stress. In conclusion, the addition of a nucleotide mixture high in 5'IMP to the diet of young pigs may be beneficial to enhance growth performance and reduce postweaning stress.