Abstract Melatonin and three of its metabolites [cyclic 3-hydroxymelatonin (3OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK)] are investigated to analyze their antioxidant capacity. The sequential scavenging action of melatonin and these metabolites has been named an antioxidant cascade, which greatly increases capacity of melatonin to scavenge free radicals and, therefore, decrease oxidative damage. In this theoretical study, we identified a new antioxidant cascade for melatonin and its metabolites by studying different antioxidant mechanisms: hydrogen atom transfer (HAT), radical adducts formation (RAF) and single electron transfer (SET). We demonstrate that melatonin and its metabolites 3OHM, AFMK and AMK are capable of scavenging free radicals through successive dehydrogenations, formation of stable radical adducts and by increasing electron donor-acceptor properties. The main conclusion in this report is that melatonin and its metabolites participate in a new antioxidant cascade and therefore scavenge many free radicals. These are new findings and help to explain the impressive ability of melatonin to reduce oxidative stress.