The association of sleep disruption with a higher vulnerability to COVID-19 infection is a subject of major clinical importance. In patients with pneumonia associated with COVID-19 admitted to non-intensive care unit (NICU) several factors, like the disrupting influence of respiratory distress, medication, greater stress due to social isolation, and lack of appropriate exposure to environmental light can be instrumental to disrupt sleep/wake cycle. The therapeutic potential of melatonin to counteract the consequences of COVID-19 infection has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. Properly administered, melatonin may restore the optimal circadian pattern of the sleep-wake cycle and improve clinical condition in pneumonia associated with COVID-19 patients. The present review article discusses the importance of maintaining normal sleep and circadian rhythmicity in NICU patients and provides preliminary data suggesting the efficacy of melatonin (9 mg/day) to reduce length of stay of pneumonia patients associated with COVID-19 in NICU.