Anaerobically fermented yeast products are a rich source of nutritional metabolites, mannanoligosaccharides, and β-glucans that may optimize gut health and immunity, which can translate into better growth performance and a reduced risk of foodborne pathogens. The objective of this study was to quantify the effects of Saccharomyces cerevisiae fermentation product (Diamond V Original XPC) inclusion in nursery diets on pig performance and gastrointestinal microbial ecology before, during, and after an oral challenge with Salmonella. Pigs (n = 40) were weaned at 21 d of age, blocked by BW, and assigned in a 2 × 2 factorial arrangement consisting of diet (control or 0.2% XPC) and inoculation (sterile broth or Salmonella). Pigs were fed a 3-phase nursery diet (0 to 7 d, 7 to 21 d, and 21 to 35 d) with ad libitum access to water and feed. On d 14, pigs were orally inoculated with 10(9) cfu of Salmonella enterica serovar Typhimurium DT104 or sterile broth. During d 17 to 20, all pigs were treated with a 5 mg/kg of BW intramuscular injection of ceftiofur-HCl. Growth performance and alterations in the gastrointestinal microbial ecology were measured during preinoculation (PRE; 0 to 14 d), sick (SCK; 14 to 21 d), and postinoculation (POST; 21 to 35 d). Body weight and ADG were measured weekly. Rectal temperature (RT) was measured weekly during PRE and POST, and every 12 h during SCK. Diet had no effect on BW, ADG, or RT during any period (P = 0.12 to 0.95). Inclusion of XPC tended (P < 0.10) to increase Salmonella shedding in feces during SCK. Consumption of XPC altered the composition of the gastrointestinal microbial community, resulting in increased (P < 0.05) populations of Bacteroidetes and Lactobacillus after Salmonella infection. Pigs inoculated with Salmonella had decreased ADG and BW, and increased RT during SCK (P < 0.001). Furthermore, fecal Salmonella cfu (log(10)) was modestly correlated (P = 0.002) with BW (r = -0.22), ADFI (r = -0.27), ADG (r = -0.36), G:F (r = -0.18), and RT (r = 0.52) during SCK. After antibiotic administration, all Salmonella-infected pigs stopped shedding. During POST, an interaction between diet and inoculation (P = 0.009) on ADG indicated that pigs infected with Salmonella grew better when eating XPC than the control diet. The addition of XPC to the diets of weanling pigs resulted in greater compensatory BW gains after infection with Salmonella than in pigs fed conventional nursery diets. This increase in BW gain is likely associated with an increase in beneficial bacteria within the gastrointestinal tract.