Plasmodium falciparum infection accelerates the senescence of erythrocytes. Senescence in hemoglobin C (HbC) erythrocytes relative to normal hemoglobin A (HbA) erythrocytes is also increased, presumably because of the sensitivity of HbC to oxidative damage and denaturation. To test for a possible increased rate of anemia in HbC individuals with malaria, we evaluated children with uncomplicated P. falciparum malaria in Bandiagara, Mali, a village with a high prevalence of HbC. The average hematocrit was significantly lower in AC children (heterozygous for HbC) than in AA children (homozygous for normal HbA). Calculated blood hemoglobin concentrations from these groups, however, showed no significant differences because of the increased mean corpuscular hemoglobin concentration (MCHC) and decreased mean corpuscular volume (MCV) of AC relative to AA erythrocytes. Average hemoglobin concentration is a better measure of oxygen delivery capacity and anemia than hematocrit value. By this measure, HbC, a malaria-protective polymorphism with few deleterious consequences, does not appear to be associated with more frequent anemia than normal HbA in episodes of uncomplicated P. falciparum malaria.