Previous studies have suggested the beneficial effects of vitamin C in patients with sepsis. However, the results could not be reproduced in the subsequent studies. This meta-analysis aimed to reevaluate the value of vitamin C treatment in patients with sepsis. Electronic databases were searched from inception to August 2019 for the studies comparing the effect of vitamin C versus non-vitamin C infusion in patients with sepsis. Data from 10 studies (4 randomized controlled trials [RCTs] and 6 retrospective studies) involving 1671 patients (495 in the vitamin C treatment group and 1176 in the control group) were included. The use of vitamin C did not reduce the risk of 28-day (OR = 0.84, P = 0.611, I(2) = 56.3%), intensive care unit (ICU; OR = 0.79, P = 0.319, I(2) = 46.2%), or in-hospital mortality (OR = 0.76, P = 0.251, I(2) = 51.0%). No difference in the duration of vasopressor usage and the length of ICU or hospital stay was present. The subgroup analysis for two RCTs suggested that vitamin C treatment showed reduced 28-day mortality (OR = 0.22, P = 0.014, I(2) = 35.7%), whereas this beneficial effect did not occur in subgroup analysis for three retrospective studies (OR = 1.11, P = 0.527, I(2) = 0%). Retrospective meta-analysis could not reveal the beneficial effect of vitamin C on patients with sepsis. Therefore, in order to clarify the role of vitamin C in sepsis the high-quality RCTs will be required in the future study.