Abstract In animals, the sympathoadrenal and hypothalamic-pituitary-adrenal axis release chemicals that can act on and alter host microbiota. Therefore, the objectives of this study were to investigate if host stress (via adrenocorticotropin and catecholamine challenge) would increase the severity of a salmonella typhimurium infection. A total of 32 nursery pigs (7.6 ± 1.5 kg BW) were selected and split into treatment groups using a 2 x 2 factorial design to examine the impacts of stress hormone challenge, S. Typhimurium challenge, and their interaction. The resulting treatment groups (n = 8 pigs/treatment) were: 1) non-challenged controls (CON), 2) stress challenged, S. Typhimurium negative (CAT), 3) stress challenge negative, S. Typhimurium challenged (SAL), and 4) stress challenged, S. Typhimurium challenged (CAT+SAL). On days post inoculation (dpi) -1, the stress challenge was initiated and continued daily until dpi 4. The stress challenge consisted of an adrenocorticotropin injection (intramuscular, 0.2 IU/kg BW), a norepinephrine injection (intramuscular, 45 μg/kg BW), and an oral drench of L-DOPA (50 mg/kg BW). On dpi 0, pigs were inoculated with a field strain of S. Typhimurium. On dpi 5, plasma was collected and all pigs were necropsied for tissue collection. Plasma and colon samples were assayed for cortisol, norepinephrine, epinephrine, and dopamine. Colon contents and the ileocecal lymph node were cultured for S. Typhimurium. At dpi 5, plasma norepinephrine, epinephrine, and dopamine concentrations were increased (P < 0.05) and plasma cortisol tended to be increased (P = 0.077) due to stress challenge. However, only colon dopamine concentrations were increased (P = 0.050) due to stress challenge. Further, CAT+SAL pigs didn’t have increased colon colonization of S. typhimurium or increased translocation to the ileocecal lymph node compared with SAL pigs. This suggests that host driven stress may not specifically exacerbate the severity of an S. Typhimurium infection.