Abstract Background There is scarce information on the human immune response to the SARS-CoV-2 infection, and on the exacerbated inflammatory reaction observed in severe COVID-19 cases. Objective To review the available evidence on the role of interferons type I and type III to SARS-CoV-2 infection. Methods We reviewed the available published evidence on the role of immune response to SARS-CoV-2 infection as well as recent publications on characteristics and outcomes of COVID-19, and their relationship with interferons type I and type III. Results The available data indicates that immune response plays an important role in controlling SARS-CoV-2 infection and the immune dysregulation can significantly modify the clinical outcomes of affected patients. In addition, the evidence suggests that IFN type I and III can play an important role in controlling viremia and modulating the immune response in COVID-19. Conclusions Due to their central role in immune response against SARS-CoV-2 infection, IFN type I and III could be considered for treatment of COVID-19.