Low levels of serum magnesium have been associated with increased polymerization and sickling and consequently vaso-occlusion (VOC) in sickle cell anemia (SCA) patients due to cell dehydration. The K-Cl co-transport plays a very important role in sickle cell dehydration and is inhibited by significantly increasing levels of magnesium. In this meta-analysis, we evaluated total serum magnesium levels in SCD patients and “healthy” controls. We pooled six studies (all from Africa and two were published in Asia).626 patients were included. The keyword used were, sickle cell disease, sickle cell anemia, and serum magnesium levels. The dichotomas data were entered manually in the most recent RevMan system(version,5.4) for metanalysis. The random effect was chosen due to the significant of heterogeneity. Funnel plot was used to assess lateralization. A P-value of <0.05 was considered significant. We found a lower serum magnesium level among patients with sickle cell disease compared to their counterparts controls, odd ratio,-.024.95%Cl,-.058--.011, Chi-square,184.07, and P-value for overall effect,0.005. A substantial heterogeneity was found, I2 for heterogeneity,98%, P-value for heterogeneity <0.001. The study shows that there is lower serum magnesium level among patients with sickle cell disease as compared to their controls. Magnesium homeostasis are altered in SCD patients, and their levels are lower in HbSS patients. Magnesium supplementation may be required to be supplemented to sickle cell anemia patients.