Abstract: The objective of this experiment was to characterize the effect of the synthetic opioid Syndyphalin-33 (SD-33) on immune cell populations with and without a concurrent inoculation with a common enteric pathogen, Salmonella enterica Typhimurium (SALM) in recently weaned pigs. On day 0, pigs (8 barrows and 6 gilts, 24±1 days of age, 8.43±0.82 kg) were weaned and fitted with jugular catheters. The following day, pigs were administered either SD-33 (0.5 μmol kg-1, given i.m.) or saline (VEH; 0.5 mL, given i.m.) and SALM (oral gavage of 5x109 CFU) or sterile broth (CON; 3 mL oral gavage) in a factorial arrangement with 4 treatment groups: VEH + CON (n = 4), SD-33 + CON (n = 3), VEH + SALM (n = 3) and SD-33 + SALM (n = 4). There were no differences in Feed Intake (FI) or Body Weight (BW) among the SALM treated animals over time (p>0.05). Cumulatively, FI among the SD-33 + CON pigs was greater(p<0.05) compared to the SD-33 + SALM pigs. White Blood Cell (WBC) populations increased (p<0.05) over the 4 days postinjection period. On day 2 postchallenge, circulating neutrophils and lymphocytes were lower (p<0.05) in VEH + SALM but not in SD-33 + SALM pigs relative to VEH + CON and SD-33 + CON pigs, demonstrating the ability of SD-33 to abrogate the affect of Salmonella. Also, on day 2 postchallenge, circulating monocyte populations were greater (p<0.05) in pigs receiving SD-33 relative to controls regardless of SALM treatment. The results of this preliminary study suggest that the opioid SD-33 may modulate the immune axis in recently weaned pigs.