The effects of partial substitution of fermented soybean meal (FSBM) for soybean meal (SBM) on immune-physiological parameters, growth performance and diarrheal incidence in neonatal calves after microbial infection were investigated. Holstein calves (n = 12) were randomly assigned to two dietary treatments: the SBM and the FSBM group. The latter group received a calf starter containing 5% FSBM instead of SBM. In order to evaluate the immunocompetence against microbial infection, all calves were challenged with porcine live vaccine by intramuscular injection at 21 days of age. The incidence and severity of diarrhea were significantly less (P < 0.05) in the FSBM group compared to those in the SBM group at 21 and 42 days of age. Feeding FSBM starter resulted in a higher (P < 0.05) relative amount of bacterial-specific IgA than those on SBM at days 5 and 14 post-microbial infection (DPMI). Viral-specific IgA also increased (P < 0.05) at 5 DPMI in the FSBM group when compared to the SBM group. The average concentration of haptoglobin of calves fed FSBM was generally higher at 3 DPMI. Our results indicate that FSBM plays a role in the alleviation of diarrhea and in the production of immune-related effector cells such as IgA and haptoglobin in calves.