Analysis of oxidative stress markers and treatment of sickle cell anemia are important to protect the people from getting affected and minimizing the level of stress to maintain a healthy lifestyle. Apart from various complications most families with sickle cell child have to bear with social problems and financial crisis. Broad spectrum multidimensional concept is Health Related Quality of life (HRQoL). A Comparative cross-sectional study was carried in 240 Diagnosed sickle cell anaemia cases (120 Homozygous SS and 120 Heterozygous AS) and 120 controls. Oxidative stress markers Malondialdehyde (MDA), SOD Superoxide dismutase, glutathione peroxidase and catalase were analysed in all subjects and data was analysed using descriptive and inferential statistics using ANOVA and statistical significance was decided by p value. Mean MDA in SS cases is 4.15 m mol/L, AS is 2.44 m mol/L, and control is 1.81 m mol/L, showing a variation across the three groups (p<.05) statistically significant. Mean Superoxide Dismutase of SS is 318.81 U/ml, AS is 252.39 U/ml, and control is 199.28 U/ml, showing a significant difference in three groups. In addition to this, the mean Catalase of SS is 34.68 nmol/min/ml, AS is 34.58 nmol/min/ml, and control is 39.69 nmol/min/ml, showing a significant difference in Catalase between the three groups (p<.05). Oxidative stress is more in homozygous than heterozygous sickle cell anemia. The HRQoL of patients of sickle cell anaemia was noted to be significantly lower as compared with the healthy controls.