Plasmodium falciparum causes 500 million clinical cases of malaria and over 1 million deaths annually. The most severe clinical manifestation of infection is cerebral malaria (CM). This neurological syndrome is thought to result from sequestration of parasitized red blood cells in the brain microvasculature and a strong inflammatory response. While numerous studies investigated the role of cytokines in CM, the role of chemokines in pathogenesis is poorly understood. Case-control studies identified the chemokine interferon-gamma-inducible protein 10 (IP-10) as a biomarker of CM. Consistent with this, we have previously shown that IP-10 neutralization and genetic deletion of this chemokine alleviates brain intravascular inflammation and protects malaria-infected mice from CM. Brain endothelial cells secrete IP-10 in response to malaria, suggesting that these cells mediate leukocyte recruitment to the site of parasite sequestration. In addition to organ-specific effects, here we found that the lack of IP-10 during infection reduces parasite biomass, suggesting that this chemokine compromises the induction of protective immunity. To identify cellular sources of IP-10 involved in these processes, wild-type and IP-10 deficient-mice were irradiated and reconstituted with bone marrow from either wild-type or IP-10 deficient-mice. Chimeric mice were infected with luciferase-expressing P.berghei and parasite biomass was assessed. Chimeras that were unable to express IP-10 in hematopoietic-derived cells (IP-10-/-→C57BL/6) had lower parasite densities than wild-type chimeras (C57BL/6→C57BL/6). Conversely, chimeras that could produce IP-10 in hematopoietic-derived cells (C57BL/6→C57BL/6) had higher parasite densities than knock-out chimeras (IP-10-/-→IP-10-/-), indicating that hematopoietic-derived sources of IP-10 have a detrimental role in controlling parasite growth. Our results suggest that the cells that produce IP-10 in response to malaria differ in the brain and lymphoid organs and that they control different processes in the two areas: leukocyte recruitment in the brain and parasite biomass in the spleen.