Abstract: BRIEF COMMUNICATION Iran J Allergy Asthma Immunol In press. A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement Zahra Alizadeh1, Nastaran Keyhanian2, Sara Ghaderkhani2, Simin Dashti-Khavidaki3, Raheleh Shokouhi Shoormasti1, and Zahra Pourpak1 1 Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran 3 Department of Pharmacology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Received: 2 January 2021; Received in revised form: 1 April 2021; Accepted: 10 April 2021 ABSTRACT No effective antiviral drugs and vaccines are available for the treatment of patients with severe coronavirus 2019 (COVID-19). Therefore, available, safe, and inexpensive drugs and supplements such as melatonin are among the proposed options for controlling inflammation. We did a randomized, single-blind study in Imam Khomeini Hospital between June 30, 2020, and August 5, 2020. Mild to moderate COVID-19 patients aged 25-65 years were eligible to enter the study based on chest CT scan, clinical symptoms, and physician diagnosis. The intervention group was prescribed 6 mg of oral melatonin for 2 weeks, which consumed half an hour before bedtime every night in low light conditions. Clinical symptoms and Creactive protein (CRP) were measured before and after treatment in the melatonin received and control (regular medications) groups. among screened patients with COVID-19, 14 patients were assigned to receive melatonin, and 17 patients were considered as controls. A significant difference (p=0.005) between CRP 1 and CRP 2 levels (before and after using melatonin) was found in the melatonin group while this difference (p=0.069) was not significant in the control group. Also, the percentage of recovery (based on symptoms) in patients who took melatonin was higher than that of patients in the control group (85.7% VS 47.1%). The result of this study confirmed the effectiveness of melatonin in mild to moderate outpatients with COVID-19. More clinical trials on elderly, diabetic, obese patients and severe cases are suggested in future studies. Keywords: COVID-19; Inflammation; Melatonin Corresponding Author: Zahra Alizadeh, PhD; Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Tel: (+98 912) 7184 258, Fax: (+98 21) 6642 8995, E-mail: z-Alizadehs@farabi.tums.ac.ir