Introduction: This study compared the levels of salivary cortisol in patients suffering from severe depression and in healthy individuals. Methods: Sample size included 30 diagnosed cases of major depression based on outdoor clinical assessment (from April 2015 to December 2105) and was established by ICD-10 and DSM-IV criteria and 30 physically and mentally healthy subjects. In this study diagnosed cases of hyperaldosteronism, Cushing’s syndrome/ disease were omitted. A predesigned proforma was created on the basis of Becks Inventory. Saliva samples were collected and processed, and the measurement of cortisol levels was done by ELISA. Results: In a normal subject, the mean cortisol level was 1.46 ± 0.9 μg/dl (Mean ± SD) whereas in depressive patients it was raised (2.2 ± 1.6 μg/dl, p=0.031). Results also showed that high level of cortisol in saliva was found in individuals with a positive family history of depression (2.3 ± 1.8 μg/dl) as compared to healthy subjects (1.5 ± 1.0 μg/dl). Mean BMI was also found to be different between the 2 groups (p=0.012). Conclusion: We concluded that salivary cortisol may act as an early diagnostic tool and non-invasive biomarker for prompt diagnosis of potential cases of depression for effective management. Hence, early initiation of treatment can be helpful in improving the late clinical consequences in severely depressed patients and decreasing the morbidity.