Background: Sickle cell disease (SCD) complications like vacoocclusionand ischemia reperfusion injury are associated with generationof reactive oxygen species with subsequent oxidative stress. GlutathioneS-Transferases (GSTs)are a group of enzymes that protect againstoxidative stress. Objective: The aim of this study is to evaluate theprevalence of GSTM1, GSTT1 and GSTP1 gene polymorphisms amonghomozygous sickle cell anemia (HbSS) patients and to investigate thepossible association between the presence of those polymorphisms andSCD severity and complications. Methods: Fifty pediatric patients withSCD and 50 controls were studied. Genotyping the polymorphisms in theGSTT1 and GSTM1 genes was performed using multiplex PCR method.The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP.Results: GSTM1 null genotype was significantly associated withincreased risk of vaso-occlusive crises (Odds ratio=1.52, 95% ConfidenceInterval= 0.42-5.56, p= 0.005). We found no significant associationbetween GSTM1, GSTT1 and GSTP1 genotypes and frequency of vasoocclusivecrises, frequency of blood transfusion, disease severity score orhydroxyurea treatment. Conclusion:GSTM1 gene polymorphism isassociated with risk of vaso-occlusive crises among Egyptian SCDpatients.