Background–   Women  are  at  a  two fold  greater  risk  for  developing  depression  as  compared  to  men. It has been found that women are vulnerable to depression during  and after menopausal transition. Alterations in endocrine and metabolic factors including monoamine deficiency, HPA and HPT axis dysfunction and inflammation and neurodegenerative alteration can be responsible for depressive disorder. So the present study was undertaken to find out the total cortisol levels in postmenopausal women with and without depression. Aims and objectives– To determine the total cortisol levels in postmenopausal women with and without depression. Materials and methods–             Fasting blood samples were analyzed for the total Cortisol levels in 30 postmenopausal females suffering from depression and 30 postmenopausal females not suffering from depression by using immunoassay technique. Results–              Serum Total Cortisol level was significantly higher in Case group (mean–37.90) as compared to Control group (mean–29.65). Conclusions–             Our findings support the hypothesis that hyperactivation of HPA axis leads to hypercortisolism  in postmenopausal women with depression .