Obesity is a worldwide health problem, and its prevalence is increasing steadily all over the globe. Leptin, mainly produced by adipocytes, was identified to modulate the immune system, as well as contributing to increased production of thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin antibody (TG-Ab). Autoimmune thyroiditis, mainly Hashimoto's thyroiditis, is believed to be the main cause of hypothyroidism in iodine sufficient regions, (TPO-Ab) and (TG-Ab) are the hallmarks of this disease. This study aimed to assess the relationship between thyroid autoimmunity, obesity and serum leptin level in a sample of Egyptian individuals. This study was a case control study which included 60 participants, recruited from the outpatient of the Internal Medicine Clinic at Ain Shams University Hospitals, during the period from February 2022 to October 2022. They were divided into two groups: Group 1 included 30 participants, have Residual hematopoiesis is an important prognostic factor of immunosuppressive therapy in severe aplastic anemia (BMI) >30 kg/m2, and Group 2 included 30 participants, have BMI (18.5-25 kg/m2). We detected serum leptin, thyroid profile and thyroid antibodies using the enzyme linked immunosorbent assay and other immunoassays. Serum levels of leptin, thyroid-stimulating hormone (TSH) and glycated hemoglobin (HbA1c) were statistically significantly higher in group 1 than in group 2 (p=0.0001 for all). Also, there was a statistically significant positive correlation between leptin level and Anti-TPO in group 1 (p=0.002). In addition, in group 1, there was a statistically significant positive correlation between serum leptin level and TSH (p=0.0001). In conclusion, there is a relationship between thyroid autoimmunity and serum leptin level in obese subjects.