This study compared the effects of partial replacement of fish meal (FM) protein with commercial soybean meal (SBM) or Lactobacillus spp. fermented SBM (FSBM) on the oxidative status and non-specific immune responses in white shrimps, Litopenaeus vannamei. A FM-based diet was used as the control. To prepare the two experimental diets, 25% of the FM protein was replaced with SBM and FSBM. Three experimental diets were fed to three groups of shrimps (initial wt: 0.63 ± 0.01 g) in a recirculating rearing system for 12 weeks. The SBM-diet group had the highest hepatopancreatic thiobarbituric acid-reactive substance value, followed by the FSBM-diet group, and the lowest in control-diet group. The activity of hepatopancreatic superoxide dismutase was highest in the control-diet group, followed by the FSBM-diet group, and was lowest in the SBM-diet group. The total haemocyte, hyaline cell, semigranular cell, and granular cell counts were highest in the control-diet group, followed by the FSBM-diet group and the SBM-fed group. Haemolymph phenoloxidase activity was higher in the control-diet and FSBM-diet groups than in the SBM-diet group. The results indicate that replacing 25% FM protein with SBM significantly reduces non-specific immune responses and induces oxidative stress in white shrimps and that FSBM prepared using Lactobacillus spp. can reduce these negative effects.