Technical Abstract: Two experiments were conducted to evaluate the effect of the iron-binding molecule lactoferrin on reducing gut populations and fecal shedding of Salmonella typhimurium in experimentally infected weaned pigs. For each experiment, crossbred barrows and gilts were purchased locally and transported to our laboratory facilities. All pigs were fed a ground starter diet available for ad libitum consumption and randomly assigned to pen (2 pigs/pen) and treatment (10 pigs/treatment; 5 pens/treatment): Control [1.25 g whey protein concentrate (WPC)/kg BW/d]; 1X lactoferrin [0.25 g lactoferrin (LF) + 1.0 g WPC/kg BW/d]; and 5X LF (1.25 g LF/kg BW/d). Experimental treatments were fed prior to inoculation via oral gavage with Salmonella typhimurium. Rectal swabs were collected daily for 4 days for quantification of the challenge Salmonella strain and scour and activity scores, and body temperatures were recorded daily following inoculation. Five days post-challenge, pigs were euthanized and tissue and luminal content samples were aseptically collected from the stomach, ileum, cecum, spiral colon, and rectum. Additional tissue samples were collected from the ileo-cecal lymph nodes, spleen, tonsil, and liver. Quantitative and qualitative bacterial culture was conducted for the challenge strain of Salmonella. No treatment differences (P > 0.10) were observed for daily fecal shedding or luminal concentrations of Salmonella in either experiment. The percentage of tissue samples Salmonella positive was not significantly different among treatments with the exception of liver tissue in Experiment I, which was lower (P < 0.05) in the 1X and 5X treatments compared to control pigs. Body weights and BW change were not affected (P > 0.10) by treatment. Following inoculation, body temperatures, scour, and activity scores were not different when examined by day or when data was combined across days. The lack of treatment effect in this experiment may be explained by the high challenge dose utilized in these experiments that may have overwhelmed any protective effect exerted by the lactoferrin. Future research should evaluate increasing the duration of feeding and/or the levels of lactoferrin fed in conjunction with a more subtle Salmonella challenge.