Using an experimental model induced by infection with the non-lethal P. yoelii 17XNL strain, and mice with a genetic deletion of Uba3 or NEDD8 in T cells, we confirmed the significance of neddylation in promoting T cell-mediated optimum IFN-γ and anti-parasite IgG responses, and thus timely control of parasitemia and host survival during Plasmodium infection. Here, UBA3 is linked to parasitic infectious disease.