Three hundred twenty newly weaned pigs (21 days of age; 6.7±0.3 kg BW) were used to determine the effects of supplementing low-complexity (LC) deoxynivalenol- (DON) contaminated nursery diets with a feed additive or fish oil on growth performance and immune response to an Escherichia coli lipopolysaccharide (LPS) challenge. Pens were randomly assigned to 1 of 5 dietary treatments (n = 8 pens per treatment): positive control (PC; contained multiple animal protein sources), or 1 of 4 LC diets (contained only plant-based protein sources) without (NC; negative control) or with ~3.5 ppm DON-contamination, without (DON-) or with a feed additive containing a blend of immune-modulating components (DON+; 2 mg/kg, as-fed) or fish oil (DONω3; 2.5%, as-fed). Dietary treatments were fed during phases I and II (7 and 15 days, respectively) and a common phase III diet was fed for 20 days. On day 22, two pigs per pen were injected IM with 30 μg/kg BW LPS and 1 pig per pen with 1 mL saline. Rectal temperatures were recorded at 0, 1, 2, 3 h after injection. At 3 h, blood was collected for plasma cytokine analysis and small intestinal histomorphology was assessed. In phase I, pigs fed PC and NC did not differ for ADG, ADFI and G:F, but these outcomes were greater than for pigs fed DON+ and DONω (P < 0.05). In phase II, pigs fed NC had greater ADG and PC had greater ADFI but lower G:F than pigs fed DON- and DONω3 (P < 0.05). At the end of phase II, pigs fed DONω3 tended to have lower BW than PC and NC (P = 0.084 and 0.079, respectively). In phase III and overall, there were no differences among dietary treatments for ADG, ADFI, G:F, or final BW. The LPS injection increased rectal temperature and reduced jejunal and ileal villus height (versus saline; P < 0.05). Plasma interferon-γ concentration was only increased by LPS for pigs fed PC, NC, and DON+ compared to the saline-injected counterparts (P < 0.05). Regardless of LPS injection, jejunal villus height was greater for pigs fed DON+ than DONω3 (P < 0.05) and ileal villus height was greater for pigs fed DON+ and PC than DONω3 (P < 0.05). Therefore, nursery diet complexity did not affect growth performance or immune response to LPS. Regardless of DON contamination and feed additive inclusion in phases I and II, pigs were able to achieve nursery exit BW not different from those fed PC. The feed additive offered marginal benefits for small intestinal villus height and immune response for pigs fed DON-contaminated LC nursery diets.