Here, we show that Akt accumulates in an inactive form during human cytomegalovirus (HCMV) infection of permissive fibroblasts, as indicated by hypophosphorylation of sites that activate Akt, decreased phosphorylation of PRAS40, and pronounced nuclear localization of FoxO3a, a substrate that remains cytoplasmic when Akt is active. Here, FOXO3 is linked to cytomegalovirus infection.