Stress and anxiety have been associated with changes in the microbiota of the gut and ultimately diminished resistance to pathogens. The objective of this study was to observe intestinal microbiota and susceptibility to Salmonella associated with stress hormones, cortisol (CORT), and norepinephrine (NE), in piglets. At weaning, 90 piglets (15 for a Salmonella challenge) were trained to take the carrier (apple juice) orally. At 2 wk after weaning, pens of piglets were assigned randomly to 1 of 3 treatments: control (CNT), NE, or CORT. Blood samples were collected prior to treatment, then piglets were dosed orally with treatments twice on day 0; at 0800 and 1600 h. Control piglets were administered 6.1 mL of the carrier only, NE pigs were administered 40 mg/mL of NE-bitartrate salt dissolved in the carrier, and CORT pigs were administered 12 mg/mL of hydrocortisone acetate dissolved in the carrier. Jugular blood samples were collected prior to necropsies (n = 5/treatment) at 0800 and 1600 h on day 1, and at 0800 h on days 2, 7, and 14 after treatments were started. A subset of pigs were subjected to a 24-h Salmonella challenge. Jejunal and ileal tissues and jejunal, ileal, cecal, and rectal contents were collected and colonies were counted. Microbial data and blood samples were analyzed using mixed models with fixed effects of treatment and day. Cortisol-treated piglets exhibited a spike in plasma CORT concentrations at 0800 h day 1 (P = 0.001) accompanied by greater concentrations of cecal Escherichia coli (P < 0.05) and a shift in intestinal environment to favor coliforms on day 2 (P < 0.05). Salmonella concentrations from rectal contents tended (P = 0.07) to be suppressed by CORT. Lactic acid-producing bacteria rectal concentrations were greater (P = 0.03) in CORT pigs on 0800 h on day 1 then NE pigs and tended to be greater than CNT (P = 0.09) and were greater on day 14 for both CNT (P = 0.003) and NE (P = 0.02). Norepinephrine spiked in NE piglets at 0800 h on day 1 (P = 0.001), 1600 h day 1 (P = 0.004), through day 2 (P = 0.04). Intestinal environment of NE pigs shifted to favor ileal anaerobes (P ≤ 0.05) and facultative anaerobes (E. coli; P = 0.01) compared to CNT. However, Salmonella concentrations in rectal contents were suppressed by NE compared to CNT (P = 0.05). Oral administration of NE and CORT had the desired effect of increasing concentrations of stress hormones and resulted in microbiome shifts throughout the intestines.