An intercellular adhesion molecule-1 polymorphism (ICAM-1^Kilifi) is present at a high frequency across sub-Saharan Africa, and its presence may increase susceptibility to cerebral malaria. Here, we report that, compared with children in whom wild-type intercellular adhesion molecule-1 is present, the incidence of nonmalarial fever is significantly lower among those homozygous for ICAM-1^Kilifi. We propose that ICAM-1^Kilifi may be associated with reduced rates of tissue damage and death due to sepsis.