Abstract Background Plasmodium falciparum and vivax are parasites responsible for most malaria cases globally. In areas where these species coexist, individuals gain protection from P vivax more rapidly, and important biological differences between species may affect immune responses. CD4 T cells are key drivers of immunity to malaria as effector and helper cells, with T follicular helper cells having key roles in antibody development. Comparative studies on CD4 T cell responses between these species are limited. Methods We assessed CD4 T cells in adults with either P falciparum or P vivax malaria. Activation and proliferation of CD4 T cells were measured ex vivo, and functional capacity was determined by intracellular cytokine staining via flow cytometry. Results The phenotype, activation, and proliferation of CD4 T cell subsets were largely comparable between species. However, within the peripheral T follicular helper (pTfh) cell compartment, there was some evidence for species-dependent activation, with relatively increased pTfh1 cells in P falciparum infection. Additionally, in P falciparum, increased IL-10 production was detected, including within IL-21–producing CD4 T cells. Conclusions While activation and function of CD4 T cells in malaria are largely comparable, some species-dependent responses are detected within the pTfh-cell compartment that may affect antibody development.