Salmonellosis remains the most frequent human food-borne zoonosis after campylobacteriosis and pork meat is considered as one of the major sources of human food-borne infections. At the farm, host heterogeneity in pig infection is problematic because high-shedders of Salmonella may contribute significantly to the spread of this foodborne pathogen in the food chain. The identification of biomarkers for high-shedders could help to control Salmonella in pigs. The purpose of the present study was to analyze immune-associated markers and composition of the faecal microbiota in pigs that shed differential amounts of Salmonella after oral infection with 109 CFU of Salmonella of 40 specific-pathogen-free (SPF) piglets. Blood and faecal samples were collected for three weeks post infection. Immune response was studied through total blood cell counts, production of anti-Salmonella antibody and TNF-, IL-1, IL-6 and IFN- cytokines using ElISA’s and gene expression. Salmonella enumeration during the 3 weeks allowed us to evaluate total Salmonella shedding for each pig, using the calculation of the area under the log curve (AULC) over 3 weeks. The hierarchical clustering of AULC value resulted in three classes, significantly different (p<0,01) corresponding to high-, intermediate- and low-shedders pigs. Faecal microbiota composition was assessed using 16S rRNA microbial community profiling and data analysis using QIIME and FROGS. All the results were analyzed between control and inoculated pigs, then between high- and low-shedders pigs. Low-shedders sero-converted earlier than high-shedders. Significant differences on the production level for IL1-β and IL6 at 1DPI and on the level expression of several host genes were observed between high- and low-shedders. Prior to infection, pigs classified later as high shedders had similar immunological profiles. Infection with Salmonella induced an early and profound remodeling of immune response in all pigs, but the intensity of the response was stronger in those that excreted high numbers of Salmonella. Some taxa of the faecal microbiota were specific to low- or to high-shedder phenotypes, whereas enrichment of several functional pathways could explain the low- and high-shedder phenotypes. This study demonstrated that host immune factors and faecal microbiota composition can be related to the level of Salmonella shedding in pigs. Influencing the microbiota by favouring certain taxa and reducing intestinal inflammation could become a strategy for preventing Salmonella high shedding.