Abstract Nutrient metabolism governs the effector functions like activation, expansion, and subset differentiation of CD4 +T-cells, the orchestrators of adaptive immunity. The levels of reactive oxygen species (ROS), the metabolic byproducts of cellular metabolism are regulated by the antioxidation pathway, which is composed of Keap1 and Nrf2 proteins. We observed that, the expression of Nrf2 is temporally regulated post-activation in CD4 +T-cells (high on day 1 and low on days 2 and 3) indicating its role in CD4 +T-cell effector functions. It is yet unknown if and how the antioxidation pathway crosstalks with cellular metabolism to shape CD4 +T-cell effector responses. Here, using mice with T-cell specific deletion of Keap1 (Keap1-KO) or Nrf2 (Nrf2-KO) we deciphered the effects of high and low levels of Nrf2 (antioxidation) levels, respectively in CD4 +T-cells. Upon activation in vitro, Keap1-KO CD4 +T-cells with constitutively high levels of Nrf2 showed higher proliferation, increased expression of early activation markers and elevated TCR-mediated signaling compared to wildtype (WT) cells. In contrast, decreased proliferation and lower TCR-mediated signaling was noted in activated Nrf2-KO CD4 +T-cells. To dissect the underlying mechanisms, we performed metabolite analyses and activation in nutrient-limiting conditions. Interestingly, activated Keap1-KO CD4 +T-cells show upregulated glutamine metabolism as measured by metabolic intermediates and rely on glutamine for optimum activation and increased expansion. Together, our findings identify a mechanism by which antioxidation protein Nrf2 metabolically reprograms CD4 +T-cells and modulates their metabolic dependencies to support their activation and expansion.