Many pathogens, including Plasmodium spp., exploit the programmed death-1 (PD-1)/PD-1 ligand-1 (PD-L1) pathway to 'deactivate' T cell functions but the role of PD-1/PD-L2 remains unclear. A definitive role for PD1 in malarial pathogenesis was established when PD1-deficient mice were shown to rapidly and completely clear P. chabaudi infections, which usually cause chronic malaria. We thus studied malarial infections to understand the relative contribution of PD-L1 and PD-L2 to immunity. We initially found that that higher PD-L2 expression on blood dendritic cells (DC), from Plasmodium falciparum-infected individuals, correlated with lower parasitemia. Mechanistic studies in mice showed that while PD-L1 expressed by DCs did indeed attenuate immune responses against malaria, PDL2 protein expressed on the same DCs improved immune responses by inhibiting PDL1–PD1 interactions. Importantly, a multimeric form of PD-L2 fused with the Fc part of immunoglobulin (PDL2-Fc), given to mice infected with lethal malaria, was sufficient to mediate survival from the lethal infection compared to control mice (92% vs 0%) and mediate survival following re-infections after several months, without additional PDL2-Fc. Overall, PD-L2 was indispensable for establishing effective CD4⁺ Th1 immunity. These studies show a new function for PD-L2, which has potential to be translated into an effective treatment for malaria and other diseases where T cell immunity is ineffective or short-lived due to PD-1.