Abstract Body: High Salt Diet (HSD) contributes to the development of hypertension through a myriad of factors including altering sodium reabsorption—namely through retention—and inducing vascular inflammation. HSD can also skew T cell populations towards the pro-inflammatory Th17 subtype which thereby furthers hypertension and end organ damage. Furthermore, salt sensitive hypertension is known to be more prevalent in women due sex hormones and chromosomes. The effect of HSD on the response to viral infection has not been previously well described. Given that Lymphocytic Choriomeningitis Virus (LCMV) produces a potent CD8 T cell response under normal conditions, we aimed to determine the effect of HSD on CD8 T Cell response to acute viral infection and whether HSD elicits sex specific differences. Male and female 5-week-old C57BL/6 mice were placed on an 8% NaCl diet and 1% NaCl water for 21 days to prior to infection with LCMV Armstrong given at 2x10^5 PFU intraperitoneally. Mice were sacrificed 8 days postinfection and flow cytometry was performed on the spleen, while end organs were collected and weighed for further analysis. Antigen-experienced T cells were defined as: CD8loCD11ahi and CD4+CD49+ respectively. HSD significantly (P< 0.001) reduced the total number of splenic CD8 T cells on day 8 following LCMV infection. Moreover, a significant reduction of antigen-experienced CD8 T cells as well as a reduction of virus-specific CD8 T cells was observed compared to standard diet (SD) infected mice (P<0.001, P<0.05). As compared to SD, HSD infected mice had increased expression of co-inhibitory receptors PD-1 and LAG3 suggesting an increase in exhaustion in splenic CD8 T cells (P<0.001). Further characterization of these receptors in antigen-experienced T cells showed increased expression as compared to naive (p<0.0001) and this upregulation suggests exhaustion of these cells in response to LCMV infection. No sex differences were observed in any splenic T cell subset. However, female heart and kidney—but not spleen—weights were significantly lower than male (P<0.05), suggesting potential differences in hypertensive end organ damage. Although T cell subtypes did not exhibit sex differences in response to LCMV infection in the spleen, our data suggests that HSD alters T cell response to LCMV infection by increasing exhaustion markers, likely resulting in reduced viral clearance which may further damage hypertensive end organs.