The objective of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in innate immune response genes with Salmonella shedding in nursery pigs. One hundred and sixty eight pigs on seven farrow-to- finish farms and one farrow-feeder operation were included in the study. On each farm, 21 pigs were selected from seven sows at weaning. Fecal samples were collected from selected pigs and cultured for Salmonella, and the isolates were serotyped. DNA was extracted from liver samples and used to genotype pigs for single nucleotide polymorphisms (SNPs) in 21 different innate immune response genes. In total, 15 (9.3%) pigs tested positive for Salmonella; the isolates from six pigs from four different litters on one farm were serotyped as Salmonella Infantis and from nine pigs from six different litters on another farm as Salmonella Worthington. SNP analysis showed an association of Salmonella shedding with a SNP in the genes encoding mannan-binding lectin (MBL)-associated serine protease-2 (MASP-2) and Toll-like receptor-1 (TLR-1) (P < 0.05). These findings suggest that Salmonella shedding in pigs is controlled by genetic elements and these genetic variants could possibly be used to breed pigs that are more resistant to Salmonella colonization and Salmonella shedding.