Objective: High-dose intravenous vitamin C (HIVC) is a major concern when treating patients with coronavi-rus disease 2019 (COVID-19). The aim of this study was to assess the clinical efficacy of HIVC on hyperinflam-mation in patients with severe COVID-19. Methods: This retrospective cohort study included hospitalized patients with severe COVID-19, a subset of whom was treated with HIVC. The medical records were screened for demographic data, laboratory findings, and medications, as well as initial and repeated values of multiple inflammatory markers for analysis. Results: A high percentage of patients presented with hyperinflammation based on inflammatory marker levels above the upper limit of normal (high-sensitivity C-reactive protein, 80.1%; interleukin-6, 91.5%; and tumor necrosis factor-a, 67.4%). Eighty-five (36%) patients received HIVC therapy. After treatment with HIVC, the levels of inflammatory markers displayed a significant decrease compared with those of patients without HIVC. Furthermore, the percentages of reduction in inflammatory marker levels were higher in patients receiving HIVC compared with those in patients treated without HIVC. Stepwise multiple linear regression analysis revealed that HIVC was independently associated with percentages of reduction in levels of inflammatory markers. Conclusions: HIVC has the potential benefit of attenuating hyperinflammation by reducing inflammatory marker levels in patients with severe COVID-19. (c) 2021 Elsevier Inc. All rights reserved.