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To evaluate the efficacy of combined vitamin C, hydrocortisone, and thiamine in patients with severe pneumonia.All consecutive patients with severe pneumonia who were treated with the vitamin C protocol (6 g of vitamin C per day) in June 2017–January 2018 (n = 53) were compared to all consecutive patients with severe pneumonia who were treated in June 2016–January 2017 (n = 46). Propensity score analysis was used to adjust for potential baseline differences between the groups.In the propensity-matched cohort (n = 36/group), the treated patients had significantly less hospital mortality than the control group (17% vs. 39%; P = 0.04). The vitamin C protocol associated independently with decreased mortality in propensity score-adjusted analysis (adjusted odds ratio = 0.15, 95% confidence interval = 0.04–0.56, P = 0.005). Relative to the control group, the treatment group had a significantly higher median improvement in the radiologic score at day 7 compared with baseline (4 vs. 2; P = 0.045). The vitamin C protocol did not increase the rates of acute kidney injury or superinfection.Combined vitamin C, hydrocortisone, and thiamine therapy may benefit patients with severe pneumonia.The vitamin C protocol was evaluated in patients with severe pneumonia.Hospital mortality tended to drop in the treatment group.The chest radiologic findings were significantly improved in the treatment group.This improvement associated independently with less hospital mortality.The treatment did not increase acute kidney injury or superinfection.