This study investigated how early life plane of milk replacer nutrition influences the resistance to an opportunistic enteric challenge with Citrobacter freundii. Twenty colostrum-fed Jersey calves were blocked by BW at birth and randomly assigned to either a low (LPN) or high plane of nutrition (HPN) treatment. The LPN calves were fed 400 and 450 g DM/d of a 20% CP and 20% fat milk replacer during the 1st wk and thereafter, respectively. The HPN calves were fed 600 and 700 g DM/d of a 28% CP and 20% fat milk replacer during the 1st wk and thereafter, respectively. All calves were challenged orally with 1 × 10⁸ cfu of a stationary phase culture of Citrobacter freundii at d 10. Fecal scores were recorded throughout the study and rectal temperatures were recorded daily beginning on d 10. Fecal and plasma samples were collected at d 10, 12, 14, 16, 18, 20, 22, and 24. Fecal samples were analyzed for DM percentage and plasma for urea nitrogen, glucose, and haptoglobin concentrations. All calves were harvested at d 24 and ileal tissues were analyzed for morphology. All data reported as LPN vs HPN, respectively. Water intakes increased to a greater extent among HPN calves after the challenge (P ≤ 0.021). There was no difference in DM percentage of feces between treatments (21.9 vs 19.9 ± 1.34%; P = 0.291) despite HPN having greater fecal scores (2.0 vs 2.5 ± 0.07; P = 0.001). Rectal temperatures were greater among the HPN calves (38.4 vs 38.6 ± 0.05°C; P = 0.024). Additionally, the HPN calves had numerically greater peak plasma haptoglobin concentrations after the challenge (266 vs 511 ± 108.0 μg/mL; P = 0.118) and a tendency to have a greater total mucosal height of the distal ileum (752 vs 921 ± 59.1 μm; P = 0.059). Therefore, these data indicate that calves fed a HPN during the neonatal period have a slightly greater acute phase response to an opportunistic bacterial enteric infection. Furthermore, these data reiterate that fecal scores should not be the only measure of enteric health, especially when evaluating the health effects associated with plane of nutrition.