Herpes simplex virus type 2 (HSV-2) increases the risk of HIV acquisition in men and overall CD4 T cell density in the foreskin. Using tissues obtained during routine male circumcision, we examined the impact of HSV-2 on the function and phenotype of foreskin T cells in Ugandan men. HSV-2 infection was predominantly associated with a compartmentalized increase in CCR5 expression by foreskin CD4 T cells, which may contribute to HIV susceptibility.