Introduction: Depression is defined as a mood disorder marked especially by sadness, inactivity, difficulty with thinking and concentration, a significant increase or decrease in appetite feeling of dejection, hopelessness, and suicidal ideation. Cortisol known as a stress hormone is found to be raised in the cases of severe depression and its higher levels were detected in saliva early morning sample. Aims and Objectives: To compare the salivary cortisol levels of normal and severely depressed patients. Materials and Methods: This study was cross-sectional, comparative and was conducted in Department of Physiology, Shaikh Zayed FPGMI Lahore in collaboration with Punjab Institute of Mental Health Lahore, after getting permission from ERB. A total 60 participants were included in this study divided equally into two groups; each group having equal number of normal and depressed individuals respectively. Patients diagnosed as having major depression based on outdoor assessment, clinically and confirmed by ICD-10 Depression Diagnostic criteria and DSM4.All known cases of hyperaldosteronism, Cushings syndrome or disease were excluded. Data was collected in the form of a questionnaire based on Becks Inventory. Saliva samples were taken, processed and assessed for cortisol levels using ELISA. Results: We found higher salivary cortisol levels in severely depressed patients. Moreover, BMI was found to be associated with depression. Cortisol levels were also found to be elevated in those subjects who had positive family history of depression as compared to normal individuals. (p-value 0.001) Conclusion: Salivary cortisol (p-value 0.03) may be considered and explored as a biomarker for diagnosis and prognosis of depression.