That the pineal gland is a source of melatonin is widely known; however, by comparison, few know of the much larger pool of extrapineal melatonin. That pool is widely distributed in all animals, including those that do not have a pineal gland, e.g., insects. Extrapineal melatonin is not released into the blood but is used locally to function as an antioxidant, anti-inflammatory agent, etc. A major site of action of peripherally-produced melatonin is the mitochondria where it neutralizes reactive oxygen species (ROS) that are generated during oxidative phosphorylation. Its role also includes major actions as an immune modulator reducing overreactions to foreign agents while simultaneously boosting immune processes. During a pandemic such as coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, melatonin is capable of suppressing the damage inflicted by the cytokine storm. The implications of melatonin in susceptibility and treatment of COVID-19 disease are discussed.
