Recurrent HSV-1 ocular disease results from reactivation of latent virus in trigeminal ganglia (TG), often following immunosuppression or exposure to a variety of psychological or physical stressors. HSV-specific CD8 ⁺ T cells can block HSV-1 reactivation from latency in ex vivo TG cultures in part through production of IFN-γ. Here we establish that either CD8⁺ T cell depletion or exposure to restraint stress permits HSV-1 to transiently escape from latency in vivo. Restraint stress caused a glucocorticoid-associated reduction of TG-resident HSV-specific CD8⁺ T cells, and a functional compromise of those cells that survive, at least partly mediated by catecholamines. Together, these effects of stress resulted in an approximate 65% reduction of cells capable of producing IFN-γ, and impairment in the ability of those cells to release lytic granules, in response to reactivating virus. We also establish that restraint stress during the primary infection results in a 54% reduction of virus-specific IL-7Rα⁺ memory precursor cells in the TG at the peak of expansion. When mice stressed early were stressed again during latency, their T cell response may be further compromised. Our findings demonstrate persistent in vivo regulation of latent HSV-1 by CD8⁺ T cells, and strongly support the concept that stress induces HSV-1 reactivation from latency at least in part by compromising CD8⁺ T cell surveillance of latently infected neurons.