Perfluorooctane sulfonate (PFOS) is an environmental contaminant that has been manufactured to be used as surfactants and repellents in industry. Due to long half-life for clearance and degradation, PFOS is accumulative in human body and has potential threat to human health. Previous studies have shown the development and function of immune cells can be affected by PFOS. Although PFOS has a high chance of being absorbed through the oral route, whether and how PFOS affects immune cells in the gut is unknown. Using mouse model of Citrobacter rodentium infection, we investigated the role of PFOS on intestinal immunity. We found at early phase of the infection, PFOS inhibited the expansion of the pathogen by promoting IL-22 production from the group 3 innate lymphoid cell (ILC3) in an aryl hydrocarbon receptor dependent manner. Nevertheless, persistent PFOS treatment in mice finally led to a failure to clear the pathogen completely. At late phase of infection, enhanced bacterial counts in PFOS treated mice were accompanied by increased inflammatory cytokines, reduced mucin production and dysbiosis, featured by decreased level of Lactobacillus casei, Lactobacillus johnsonii and increased E. coli. Our study reveals a deleterious consequence in intestinal bacterial infection caused by PFOS accumulation.