Introduction: Altered cortisol secretion in the form of Cortisol Awakening Response (CAR) is one of the consistent features in patients with depression. Evidence suggests that antidepressant treatment might alter cortisol indicators in patients with depression. Aim and Objectives: This study was aimed to evaluate the changes in morning and evening salivary cortisol indicators in patients with major depressive disorders, who had received antidepressant treatment. Methods: The participants were sixty-four diagnosed cases of major depressive disorders according to Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria, who were taking antidepressant medications from different groups for at least one month. The salivary cortisol values were taken as morning and evening samples at baseline and two follow up at two months intervals and compared by student__ampersandsignrsquo;s t-test. Results: A significant difference (p__ampersandsignlt;0.0001) was noted in the mean salivary cortisol levels (morning and evening)at baseline and subsequent follow-up. Conclusions: Morning and evening salivary cortisol concentrations were increased in patients with MDD. Antidepressant treatment resulted in the alteration of cortisol indicators.