This study was to evaluate effects of soy protein concentrate (SPC) supplementation replacing animal protein supplements on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, mucosa-associated microbiota, and growth performance of nursery pigs. Thirty-two newly weaned pigs at 21 d of age with 6.4 ± 0.4 kg body weight (BW) were allotted to 4 treatments in a randomized complete block design with initial BW and sex as blocks. Pigs were fed for 35 d in 3 phases. Dietary treatments were SPC 0% (diets with fish meal 4/2/1%, poultry meal 10/8/4%, blood plasma 4/2/1%, and crude protein 24.6/22.6/20.9% for phase 1/2/3, respectively), SPC 33%, SPC 66%, and SPC 100% (SPC 0% diets with SPC replacing 33/66/100% of animal protein supplements, respectively). Pigs were euthanized on d 35 to collect jejunal mucosa and tissues to evaluate intestinal immune status, intestinal oxidative stress status, intestinal morphology, and mucosa-associated microbiota in the jejunum. Titanium dioxide was added in phase 3 diets as an indigestible marker. Ileal digesta was collected to measure apparent ileal digestibility (AID) of nutrients. Data were analyzed using MIXED and NLMIXED procedure of SAS. Increasing SPC supplementation replacing animal protein supplements linearly decreased (P < 0.05) the BW, ADG, and ADFI of pigs during the overall period, and linearly increased (P < 0.05) peptide tyrosine tyrosine (PYY) in jejunum. Increasing SPC supplementation linearly decreased (P < 0.05) feed cost per weight gain. In exponential model, SPC can replace animal protein supplements up to 10.5% and 16.5% without reducing the ADG and ADFI of pigs, respectively. The SPC 100% decreased (P < 0.05) Helicobacteraceae, Campylobacteraceae, alpha diversity, and changed beta diversity of microbiota in the jejunal mucosa. In conclusion, SPC supplementation replacing animal protein supplements reduced growth performance by reducing feed intake, which might be related to increased PYY. However, 10.5 and 16.8% animal protein supplements can be replaced by SPC without affecting BW gain and feed intake of nursery pigs, respectively. Complete removal of animal protein supplements by SPC supplementation modulated the composition of jejunal mucosa-associated microbiota by reducing Helicobacteraceae and Campylobacteraceae, whereas without affecting the intestinal immune status, intestinal oxidative stress status, intestinal morphology, and AID of nutrients in nursery pigs.