Abstract Effective T cell responses depend on adhesion mechanisms that guide T cells to sites of infection and inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to impact T cell migration; however, its role in the differentiation of responding T cells has not been investigated. Since PSGL-1 is highly expressed on naïve, effector, and memory T cells with varying degrees of glycosylation that impact ligand binding, we hypothesized that PSGL-1 may regulate T cell fates. Using mice deficient in PSGL-1 and three murine models we found that PSGL-1 limits the magnitude of the ensuing T cell response. PSGL-1-deficient mice had an increased accumulation of anti-viral CD4+ and CD8+ T cells after both acute and chronic LCMV infection. Virus-specific PSGL-1-deficient T cells had enhanced survival and were not hyper proliferative. Furthermore, PSGL-1-deficient T cells had superior effector function, downregulation of PD-1 and other inhibitory receptors, and enhanced viral control. The enhanced T cell response resulted in significant mortality of PSGL-1-deficient mice infected with chronic LCMV, whereas all PSGL-1-deficient mice survived the acute LCMV infection. After viral clearance, more CD4+ and CD8+ PSGL-1-deficient T cells survived to form memory cells. Interestingly, resting memory T cells from PSGL-1-deficient mice sustained PD-1 downregulation implying that PSGL-1 may regulate inhibitory receptors in memory T cells. We found that PSGL-1-deficient T cells had superior function in a tumor model and were more effective in controlling melanoma tumors. Our findings in three separate models show a previously unrecognized role for PSGL-1 in negatively regulating T cell responses and may have high therapeutic potential.