SUMMARY Vitamin D supplements have been suggested as being useful in high doses for preventing and treating severe disease associated with SARS-CoV-2 infection (i.e. COVID-19). Vitamin D status has been shown to be low in patients with acute respiratory infections. Unfortunately, it is yet unclear whether those associations are causal. Currently, the mechanisms underlying the effects of vitamin D in the lung are not completely understood. In addition, there is not data that demonstrates that vitamin D or the active form of vitamin D (1,25(OH)2D, 1,25D) is effective for improving outcomes following a viral infection. The effects and timing of supplemental vitamin D will be tested on host resistance to SARS-CoV-2 infection in mice and hamsters. The basic mechanisms by which vitamin D regulates the immune response following a respiratory virus infection are critical for the safe and effective messaging for vitamin D supplementation. Understanding the mechanisms underlying the effects of vitamin D in the lung is needed to provide responsible guidance on whether it is safe and effective to supplement individuals with high amounts of vitamin D to protect from COVID-19 disease.