Background Thiamine and vitamin C have been increasingly used in patients with sepsis or septic shock because of their potential for improving metabolism and reducing mortality. Objective We aim to determine if thiamine combined vitamin C can reduce mortality in patients with sepsis or septic shock. Evidence sources and study selection We comprehensively searched the PubMed, Embase, Cochrane Library, and Web of Science databases from their inception dates through 1 January 2021. Literature works evaluating the efficacy of thiamine combined vitamin C in patients with sepsis or septic shock were considered. Data extraction and outcome measurements Two reviewers extracted data and assessed study quality. A meta-analysis was performed to calculate an odds ratio (OR), 95% confidence intervals (CIs), and P values for in-hospital mortality (primary outcome). Secondary outcomes included duration of ICU stay, duration of hospital stay, duration of vasopressor use, and change in sequential organ failure assessment (SOFA) scores. Results Seven randomized controlled trials were identified, encompassing a total of 868 patients. There was no statistical difference between groups for in-hospital mortality (OR: 1.11; 95% CI [0.79–1.56]; P = 0.55). Other than improving SOFA score during the first 72 h after enrollment and duration of vasopressor use, we found no other significant associations. Conclusions: Despite widespread enthusiasm for thiamine combined with vitamin C for sepsis and septic shock, we only found an association with reduced SOFA score and time of vasopressor use. There was no association with in-hospital mortality.