The species P. vivax and P. falciparum account for most human infections, yet little is known about P. vivax specific immune responses and whether they are similar to or distinct from P. falciparum. Here, we establish that P. vivax and P. falciparum elicit distinct cellular immune responses following primary infection, with the expansion of a subset of CD38+ CD8+ T cells with a cytotoxic potential in P. vivax but not in P. falciparum infection. The gene discussed is CD38; the disease is infection.