Depression (MDD) is a major global health problem. The number of people suffering from major depressive disorder was reported as around 300 million (about 4.4% of the world's population) in 2015. The total number is assumed to increase to 18.4% from 2005 to 2015. Depression is more common in females compared to males (female: male = 5.1:3.6). Years lived with a disability are about 50 million people due to major depressive disorder and this disease has been claimed to be a major cause of morbidity, mortality, and also suicidal death. In Bangladesh, the prevalence of depressive disorder is about 4.1% and the percentage of total years lived with a disability (DALY) is about 7.1%. Within this number, some people suffer additionally from anxiety disorders and some suffer from both anxiety disorder and MDD. However, MDD has been assumed to occupy the place of the second cause of disability by 2020, and MDD, therefore, demands attention and alerts in clinical psychiatry. Depression impairs quality of life at the level of personal, familial, and social aspects and in the severe form, may lead to thoughts of committing suicide. Suicidal death (about 8,00000 per year) have been reported throughout the world in recent reports and are increasing gradually. Conventional antidepressants are the medicines used to treat MDD. Increasing 5HT concentrations at the synapses of the amygdala, frontal cortex, or the limbic region by SSRI or TCA or other drugs administration remains the primary object of therapy. About 19-34% of MDD patients show a reasonable level of response to the SSRIs while about 15-50% of patients show dissatisfactory response or recurrence. This fact is a subject of concern and invite pharmacological intervention either in the form of adjunct drugs or new drug discoveries. Recent researches have revealed that a significant role of zinc in MDD patients due to its antidepressant effects. Some studies reported that there is no effect of zinc supplementation on depression in MDD patients. Because of the conflicted reports, this study has been designed to evaluate the effect of zinc supplementation on depression in MDD patients treated with SSRI. Results of this study may be helpful to advocate the regular use of zinc supplementation as an adjunct to SSRI therapy in MDD. The study would be randomized, double-blind, placebo-controlled prospective interventional trial and it would be conducted in the Department of Pharmacology and in collaboration with the Department of Psychiatry, BSMMU, from the date of approval by the IRB to August 2020. A total of 100 patients suffering from mild to moderate major depression will be selected following to inclusion and exclusion criteria and serum Zinc levels will be assessed. The diagnosis of patients suffering from MDD and the selection of drugs and dosage would be performed by a senior professor of the Psychiatry department. After completing the necessary formalities including the informed consent of the patients, the patient would undergo a selected questionnaire (DASS-21) to assess his/her degree of severity of the disease. The patients would be randomly allocated into two groups: group A (control group) and B (intervention group). Group A would consist of 50 patients who will receive a placebo with SSRIs for 8 weeks. Group B would consist of 50 patients who will receive SSRIs plus Zinc sulfate (30mg/day) orally for 8 weeks, after which at follow up, the severity of depression will be assessed. The blood sample will be collected to measure serum zinc level at baseline and again after 8 weeks of therapeutic intervention. The regularity of medicine intake will be ensured over the telephone, counting the tablets, and from the patient's compliance sheet. The study entails almost no potential risk to the patients which will be explained to the patients together with the fact that he/she would be free to leave the study at any time and that he/she would receive free of cost treatment in case of any adverse reactions. Statistical analysis will be obtained by SPSS (Statistical Package for Social Science). Results will be presented in tables and graphical figures as applicable. Calculated 'p' value may suggest the level of significance (significant at p ≤ 0.050). The study will follow the principles of the Declaration of Helsinki and of the World Medical Assembly. Patients will be informed about the study in easy language and then informed consent will be taken. The study has no potential risk to the patients. Confidentiality will be strictly maintained.