Malaria remains a major public health problem worldwide. The immune mechanisms that mediate protection against malaria are still unclear. Previously, we reported that mesenchymal stem cells (MSCs) play a critical role in host protection against malaria by altering the dynamic balance of T regulatory cells and effector T cells producing inflammatory cytokines. Here, we report that MSCs reprogram haematopoiesis in primary (bone marrow) and secondary (spleen) lymphoid organs to provide host protection against malaria. Adoptive transfer of MSCs from malaria-infected mice to naïve recipient mice that were subsequently infected with malaria parasites dramatically accelerated the formation of colony-forming units-erythroid cells in the bone marrow. Adoptively transferred MSCs also induced expression of the key erythroid cell differentiation factor GATA-1 in the spleen of recipient animals. Interestingly, we further observed a subtle increase in the CD34+ hematopoietic stem and progenitor cells in lymphoid organs, including spleen and lymph nodes. Infusion of MSCs also enhanced T cell proliferation, resulting in increased numbers of both CD4+ and CD8+ T cells in the spleen. MSCs also inhibited the induction of the negative co-stimulatory receptor programmed death-1 by T cells in recipient animals upon infection with malaria parasites. Taken together, our findings suggest that MSCs play a critical role in host protection against malaria infection by modulating erythropoiesis and lymphopoiesis.