Both sickle-cell anemia and G6PD deficiency are red blood cell gene abnormalities that cause hemolytic anemia. Their association may have serious consequences. The objective of this study is to determine the prevalence of such an association at the CNRD of Niamey and the impact of G6PD on sickle-cell anemia patients. A prospective cross-sectional study was conducted with 227 major sickle-cell anemia patients in stationary phase by comparing hematological parameters, free and total bilirubin concentrations, impaired hepatic and splenic functions as well as hospitalization and blood transfusion rates. G6PD intra erythrocytic was determined by spectrophotometry at all sickle cell patients on the hemolysate of washed red blood cells. Findings were analyzed by Epi-info 3.5.4 and the significance level was set at P < 0.05. G6PD was found in 7.08% of sickle-cell anemia patients. SS sickle-cell anemia was the most frequent form of the disease (83.3%). Hb levels as well as reticulocyte rates and MCHC were not significantly different in both groups of major sicklecell anemia patients. But, the level of total bilirubin was significantly high in sickle-cell anemia in case of G6PD deficiency. Though the risk of hospitalization was similar in both groups of patients, sickle-cell anemia patients with G6PD deficiency were more likely to develop hepatomegaly or splenomegaly.