Sickle cell anemia is a chronic, inherited hemoglobinopathy disease that has a high morbidity and mortality. Zinc has a crucial role in immunity and growth, which are affected in these patients. This review evaluated the zinc level in sickle cell anemia patients. Cochrane Library, PubMed, Medline, and Google Scholar were searched and limited to the period from January 2012 to December 2022. The keywords "zinc levels," "sickle cell disease," "serum zinc," "sickle cell anemia," and "urinary zinc" were used. Out of the 353 studies, 76 full texts were screened, and only thirteen studies were included in the final analysis. The author's name, year of publication, patient's number, and study duration were collected and entered in an excel sheet. The RevMan system for meta-analysis was used, and the data were all continuous. The random effect was used due to the significant heterogeneity. Funnel plots were used to assess lateralization. A P-value of <0.05 was considered significant. The studies included 1513 patients and control subjects. In case-control studies, zinc levels were lower in patients with sickle cell disease; the odd ratio was -10.88, the 95% CI was -16.27—5.49, and the P-value for the overall effect was 0.0001. The cross-sectional studies showed the same, odd ratio, -22.07, 95% CI, -30.15—13.99, and the P-value for the overall effect, <0.0001. This review showed that the zinc level is low in sickle cell anemia patients compared to normal children, which has a negative impact on the disease. Randomized control studies are needed.