Background and Objective: SARS-CoV-2 plays with an individual’s immunity and the severity of the infection depends on patient’s immuno-competence. While it is well known that nutritional deficiencies can impair the immune system, making it particularly susceptible to infections, evidence on the efficacy of Vitamin supplementation in the prevention and management of viral infections is still fragmented. Therefore, we conducted a systematic review aimed at summarizing the clinical effects of vitamin supplementation against SARS-CoV-2 infections. Methods: PubMed, Scopus, and Web of Science were searched. RCTs comparing the effects of any vitamin supplementation in any form vs. placebo or standard of care in the prevention and/or management of confirmed SARS-CoV-2 infection in people of any age were included. A narrative synthesis of the Results was conducted. The revised Cochrane Risk-Of-Bias tool was used to assess quality. Results: A total of 10684 records resulted from the initial search, of which 30 RCTs were included. Two studies investigated the administration of multivitamin complexes, 20 the administration of vitamin D, whereas eight the administration of vitamin C. Four studies evaluated the prevention of SARS-CoV-2 infection in high-risk individuals. Prevention of Long COVID was studied by only one author. The populations under investigation were mainly hospitalized. Preliminary results indicated that findings were heterogeneous in relation to the clinical management of patients included, whereas no significant results were found in the prevention area. Individuals supplemented with vitamin D had a better prognosis. The most studied outcome was mortality, which appeared significantly reduced especially in the case of vitamin D supplementation. Conclusions: Despite the initial stage, we found that differences in populations considered, as well as variety in recruitment and treatment protocols, highlight the need to conduct further investigations to estimate the clinical benefits of vitamin administration in COVID-19 patients.