SARS-CoV-2 expanded worldwide since December 2019, and COVID-19 has emerged with many unknown facets. The evidences suggest that COVID-19 is a multisystem disorder, affecting ubiquitous targets, in which oxidative stress and inflammatory process play relevant roles. The lack of a specific antiviral therapy had led to the situation of finding supportive alternatives to prevent or to treat COVID-19. Previous research suggested the role of vitamin supplementation to attenuate the severity of respiratory infections and to augment the immune system via antioxidant properties, in order to prevent the development of severe forms. Vitamin C acts as a potent antioxidant and restores the level of others, improving the immune functions. Its low level correlates with respiratory infections, including COVID-19 and its supplementation ameliorates the symptoms and shortens the duration of infections. Vitamin D activates the immune response reducing the risk and severity of respiratory infections in patients with low plasmatic level, but its preventive role in healthy people is not well established. Recent data showed higher levels of vitamin D during the pandemic vs pre-pandemic, probably due to a lower demand for it in immunomodulatory processes. Dietary interventions may represent an add-on strategy in preventing and treating respiratory infections, including COVID-19.