The underlying rationale to investigate the therapeutic potential of vitamin C has been based on two key observations: (i) critically ill patients have lower levels of vitamin C (228–230) and (ii) vitamin C has pleiotropic immunomodulatory, antioxidant, and antiviral effects (221). It is important to underscore that reports on the clinical outcomes of vitamin C treatment in humans are mixed and context dependent. A thorough meta-analysis on vitamin C supplementation for the common cold has been reported by Hemilä and Chalker (231). Briefly, they concluded that while the incidence of colds was not reduced, the duration and severity of colds was reduced when assessing studies of regular vitamin C intake (231). Interestingly, a separate meta-analysis on vitamin C and cardiac surgery showed a reduction in the length of ICU stay and shortened the need for mechanical ventilation (232). This is an important correlation as clinical trials are currently investigating the efficacy of vitamin C to reduce mortality and hospital burden in COVID-19 patients (Table 1). A Phase II clinical trial (NCT04264533) was initiated in Wuhan where COVID-19 patients will be given a high dose intravenous infusion of vitamin C. Lastly, whether oral dosing of vitamin C can achieve therapeutically relevant concentrations, as described in the above studies, is currently unknown, thus caution should be taken as exceeding the recommended dietary allowance of 100–200 mg/day may lead to mild toxicities including abdominal discomfort and diarrhea (231, 233).