While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells and type 1 responses, this immunity cannot be found in the circulation after immunization. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of CD4+ T cells that are transcriptionally active for ifng gene and could passively transfer protection, but only transiently. Circulating Salmonella-reactive CD4+ T cells highly expressed the liver-homing chemokine receptor CXCR6, accumulated over time in the liver and assumed dysfunctional characteristics associated with tissue-resident memory (Trm) T cells when ex vivo. Effector and resident Th1 subsets differ on the expression of a variety of membrane molecules, including CD69, KLRG1, CD101, LFA-1, P2rx7, ARTC2. Liver memory T helper 1 (Th1) cells showed enhanced reactivity for S. Typhimurium antigens after specific inhibition of P2rx7-mediated loss of functionality and preferential usage of TCR Vβ chains. Parabiosis and adoptive Trm transfer experiments demonstrated that non-circulating memory pools are important for optimal protection to lethal Salmonella strain. Our systematic study showed that CD4+ T cell-mediated immunity to Salmonella infection is circulant, but this is limited to a brief window during which Salmonella-specific CD4+ T cells migrate to peripheral tissues where becomes resident. Our observations are supported by volunteer studies of vaccination and highlight the importance of triggering tissue-specific immunity against systemic infections.