Soybean meal (SBM) inclusion is reduced in young pig diets due to antinutritional factors that may negatively impact performance and gut function. However, when SBM is fed to grower pigs under disease or environmental stress, health may improve through modulation of immunity. Presently it is unknown if a parallel effect will be realized in nursery pigs. Therefore, the experimental objective was to examine the role of SBM and its bioactive compounds on nursery pig gastrointestinal physiology, systemic health, and inflammatory markers. Two replications of 18 barrows (8.12 ±0.80 kg BW; PIC800×Camborough), were randomly assigned to 1 of 6 dietary treatments: a high SBM positive control (SBMC; 28.6%), a negative control void of SBM (SP), but included soy protein isolate and concentrate to provide amino acids equivalent to SBM in SBMC; SP formulated to similar contribution and composition of isoflavones as SBMC (SP+ISO; 528 mg/kg of soy isoflavones); SP diet fortified with soybean lecithin and phytosterols at similar concentrations to SBMC (SP+LIP; 2.85 g/kg of functional lipids); SP formulated to an equivalent ratio of insoluble to soluble fiber as SBM in SBMC (SP+FIB; 30 g/kg of soy fiber); or SP diet fortified with lunasin-peptide at 3.81 g/kg (SP+LUN). Pigs were individually housed, and limit fed 2.5 times maintenance for a metabolism study consisting of a 6-d adaptation period, followed by 72-h of urine and fecal collections, and a 12-h lactulose:mannitol test. On d 11, whole blood and serum were collected prior to feeding, and at 2, 5, and 24 h post-feeding via jugular-venipuncture. Serum was analyzed for total antioxidant capacity (TAC) and malondialdehyde (MDA). Hematology was measured on whole blood. On d 12, pigs were necropsied for intestinal tissues collection. Data were analyzed as a linear mixed model with treatment as a fixed effect, replicate as a random effect, and initial BW as a covariate where appropriate. A dependent covariance structure was used for repeated measurements. Pigs fed either SBMC or SP+LIP had greater mean corpuscular volume and hematocrit % (P=0.027). Relative to the SP diet, pigs fed SP+LIP tended to have 11.4% greater hemoglobin concentrations (P=0.086). Circulating total white blood cells (WBC) were 21.2% and 22.6% lower in pigs fed SBMC and SP+ISO diet, respectively, relative to SP (P=0.002). Similarly, SBMC and SP+ISO had reduced neutrophil counts (P=0.043). Relative to SP, SBMC, SP+ISO, and SP+FIB tended to have increased systemic TAC (P=0.086). Pigs fed either SBMC or SPC+ISO had over a 2-fold increase in the TAC of the jejunum, relative to SP (P=0.039), but those fed SPC+FIB had increased TAC in the ileum and reduced MDA (P<0.05).