T cell metabolism increases upon activation, underpinning immune effector functions. Nicotinamide adenine dinucleotide (NAD/H) is an essential redox cofactor for glycolysis and mitochondrial substrate oxidation. It is also phosphorylated to NADP/H, which regulates reactive oxygen species (ROS) abundance. NAD/H levels increase upon T cell activation, but synthesis pathways and implications are not fully characterised. Here, we interrogated the role of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1), the expression of which increases upon human and murine CD4+ T cell stimulation. Functionally, NRK1 activity restrains CD4+ T cell activation and cytokine production and promotes survival. These activities are linked to increased NRK1 expression in the cytoplasm, where it locally elevates NAD/H levels. This supports glycolysis, but more profoundly impacts cytoplasmic NADP/H generation, thereby controlling ROS abundance and nuclear NFAT translocation. During invasive fungal infection, T cell-intrinsic NRK1 maintains effector CD4+ T cell frequencies within affected tissues, thereby permitting infection control. Taken together these data confirm that subcellular regulation of immune cell metabolism determines whole organism immune responses.