Human parvovirus B19 (HP-19) is the only Parvoviridae known to be pathogenic in human. Studies of HP-19 infection and its associated life-threatening complications in sickle cell anemia patients have been reported in Europe and the US. These results justify the development of HP-B19 prevention and strategies to reduce the incidence of severe and life-threatening complications associated with the infection in patients with sickle cell anemia, particularly in sub-Saharan Africa where the sickle cell anemia burden is high. In light of these considerations, we conducted a case–control study including 163 patients with sickle cell anemia and 163 controls. HPB19 diagnosis was based on the detection of IgG and IgM antibodies specific for HP-B19 using commercially available enzyme immunoassays. Anti-human parvovirus B19 IgG antibodies were found in 105 of 193 (64.8%) patients vs 79 of 193 controls (48.4%). IgM antibodies were found at a higher frequency in sickle cell anemia patients than in controls. This higher frequency was found to be age dependent. However, the reticulocyte count showed no significant decrease in Malian patients with sickle cell anemia. Further studies are needed to better characterize the implication of HP-B19 infection in sickle cell anemia mortality and morbidity and to develop preventive strategies and efficient management of the resulting complications.