Malaria, caused by Plasmodium parasites, is a highly prevalent and devastating disease that can persist for years. There has been considerable difficulty in developing a malaria vaccine, highlighting our incomplete understanding of immunity against this disease. Antibodies and CD4+ T cells are thought to protect against blood-stage infections. We used an experimental rodent malaria model, to show that programmed death-1 (PD-1) mediates a 95% reduction in numbers and functional capacity of parasite-specific CD8+ T cells during acute malaria, driving chronic disease. Furthermore, we demonstrated PD-1 also affect CD4+ T cell function that, improved effector CD4+ and CD8+ T cell function during the chronic phase of infection, compared to wild-type mice. Importantly, in contrast to widely held views, parasite-specific CD8+ T cells are required to control both acute and chronic blood-stage disease even when parasite-specific antibodies and CD4+ T cells are present. Our findings provide a molecular explanation for chronic malaria which will be relevant to future malaria-vaccine design and may need consideration when vaccine development for other infections is problematic.