We show that assessing the plasma proteome of the major malaria syndromes provides an unbiased discovery of combination of proteins that could be used to deepen our understanding of the pathogenesis of childhood malaria. This is supported by the finding that we can discriminate children with uncomplicated malaria from those with severe malarial anemia or cerebral malaria in both discovery and validation cohorts. These proteomepatterns encapsulate what changes differentiate uncomplicated malaria from the severe cases.