This study investigates the relationship between copeptin levels, thyroid hormone concentrations, and body mass index (BMI) in patients with goiter. The experiment was conducted from the beginning of April 2023 until the end of September 2023, and samples were collected from Azadi Teaching Hospital in Kirkuk City. Sixty blood samples were collected and divided inti two groups: 40 patients with goiter and 20 healthy individuals. The samples analyzed for copeptin and thyroid hormones (T3, T4, and TSH) using enzyme–linked immunosorbent assay (ELISA) and results revealed significantly higher levels of copeptin, T3, T4, and TSH in goiter patients compared to controls, smoking was found to exacerbate thyroid dysfunction, as smoker tend to have higher levels of copeptin and thyroid hormone compared to non-smokers, and patient with goiter were observed to have a significantly higher BMI, highlighting the complex relationship between thyroid dysfunction, smoking, and metabolic processes. In goiter patient elevated copeptin levels were associated with increased metabolic activity, activation of the hypothalamic- pituitary- adrenal (HPA) axis, and heightened systemic inflammation. The study also examined the role of smoking- induced oxidative stress and inflammation in driving these changes.