Abstract Inhibitory signaling in dysfunctional CD8 T cells through the PD-1 axis is well established in chronic viral infections and cancers. PD-1 is also transiently induced to high levels during priming of acute infections and immunizations, yet its impact on the development of long-lived antigen-independent T cell memory remains unclear. Here we show that in addition to its expected role in restraining clonal expansion, PD-1 expression on antigen-specific CD8 T cells during priming and activation is critically required for the development of a durable CD8 T cell memory pool after antigen clearance. Loss of T cell-specific PD-1 signaling led to increased contraction and a striking defect in antigen-independent renewal of memory CD8 T cells in response to homeostatic cytokine signals, thus resulting in attrition and near ablation of the memory pool over time. Notably, in the setting of PD-1 checkpoint blockade immunotherapy of chronic viral infection, while the exhausted CTLs expectedly regained function, the pre-existing pool of resting functional memory cells established in response to a previously administered vaccine underwent attrition. Metabolically, PD-1 signals were necessary for regulating the critical balance of anabolic glycolysis and fatty acid oxidation programs through mTOR to meet the bioenergetics needs of quiescent memory. These studies define PD-1 as a key metabolic regulator of protective T cell immunity, and have potential clinical implications for pre-existing T cell memory to prior infections and vaccinations during PD-1 checkpoint-blockade immunotherapy in cancer.