|Non-typhoidal members of the genus Salmonella are important bacterial zoonoses, causing significant burden in both developed and developing countries. While the epidemiology of gastrointestinal infections caused by non-typhoidal Salmonella (NTS) is extensively studied in developed countries, there is a paucity of data regarding the source of and potential transmission routes for NTS infections in developing countries. Given the high density of human and animal populations living in close proximity in southern Vietnam, as well as the predominance of backyard, mixed-species animal production systems with little investment in biosecurity, the role of human-animal contact in NTS transmission warrants further research in this region. This study assesses the impact of differential human-animal contact rates and contact with different livestock species on exposure to NTS among individuals living in Tien Giang, a province located in the Mekong Delta region of southern Vietnam. Concentrations of antibodies specific to Salmonella enterica serovars Typhimurium and Enteritidis in serum from individuals living in this province were quantified using enzyme-linked immunosorbant assays (ELISAs) in order to gauge the level of exposure to NTS at the human-animal interface in this region. Significantly higher antibody concentrations were found for individuals who report routine contact with duck species than those who do not. This finding identifies duck exposure as an important factor associated with past infection, and highlights the importance of targeting intervention efforts at duck reservoirs and the need for future research identifying specific husbandry practices and flock characteristics that promote NTS transmission between ducks and humans in order to better target these efforts. Significant differences in antibody concentrations among individuals living in farm, urban, and rural settings were also identified. Given recent studies identifying an important role for antibody production in the development of protective immunity to NTS, this finding provides support for the hypothesis that increasing urbanization may result in lower levels of population immunity, with important implications for the burden of human cases of salmonellosis in years to come. This study highlights the importance of understanding the influence of agricultural practices and changing human demographics on the transmission and epidemiology of zoonoses of public health importance.