Aims: To find out the correlation between Osteopontin (OPN), oxidative stress and total antioxidant capacity (TAC) in female hypothyroidism subjects. Study Design: Case Control study Place and Duration of Study: The present case control study was conducted with the collaboration of the Department of Biochemistry, Santosh Medical college, Ghaziabad and Muzaffarnagar Medical College, Muzaffarnagar from September 2018 to September 2020. Methodology: The study includes 120 female hypothyroidism subjects and 120 age and sex matched normal healthy individuals as controls.  Serum OPN was estimated by commercially available ELISA kit, MDA by method described by Satoh et al. method, TAC by FRAP method and Ceruloplasmin was estimated on Access 2 Beckman Coulter clinical chemistry analyser. Results: The anthropometric parameters, Body mass index (BMI), waist circumference (WC), hip circumference (HC) and waist hip ratio (WHR) were increased significantly in all the female hypothyroidism subjects as compared to controls. Study showed increased levels of TSH and MDA and decreased levels of serum Osteopontin, T3, T4, TAC and Ceruloplasmin (Cp) in hypothyroid subjects as compared to controls. A Significant positive correlation was found between OPN vs T3, OPN vs T4, OPN vs TAC and OPN vs Cp whereas significant negative correlation was found between OPN vs TSH, and OPN vs MDA. Conclusion:  In the present study, we found decreased levels of Osteopontin in hypothyroidism subject. Pearson’s correlation analysis predicts, OPN negatively correlated with MDA and positively correlated with total antioxidant capacity and ceruloplasmin. Hence, Osteopontin, malondialdehyde, total antioxidant capacity and ceruloplasmin should all be considered while assessing the hypothyroidism.