Background: Recent clinical trials have investigated the use of fluvoxamine in preventing clinical deterioration in nonhospitalized patients with acute COVID-19 infection via stimulation of sigma-1 receptors, which regulates cytokine production and functional inhibition of acid sphingomyelinase activity, which may prevent infection of epithelial cells with SARS-CoV-2. However, the role of fluvoxamine is currently unclear because of a paucity of studies, particularly because the drug is being repurposed as an immunomodulatory and antiviral agent., Study Question: Aim of our meta-analysis was to investigate the efficacy of fluvoxamine in nonhospitalized patients with acute COVID-19 infection., Data Source: Comprehensive literature search of PubMed, Embase, Cochrane Library databases, and Web of Science was performed from inception to February 10, 2022, for studies comparing fluvoxamine versus placebo for outpatient management of COVID-19., Study Design: The primary outcome of interest was rate of hospitalization. The secondary outcomes were rates of patients requiring mechanical ventilation and mortality. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A P value <0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index., Results: Three studies (2 randomized controlled trials and one prospective cohort trial) involving 1762 patients were included in the meta-analysis. In patients who received fluvoxamine compared with placebo, there was no significant difference in rates of hospitalization (RR 0.26, 95% CI, 0.04-1.73, P = 0.16, I2 = 62%), mechanical ventilation (RR 0.73, 95% CI, 0.45-1.19, P = 0.21, I2 = 0%), and mortality (RR 0.67, 95% CI, 0.37-1.22, P = 0.19, I2 = 0%)., Conclusion: Current evidence does not indicate a significant effect of fluvoxamine on the rates of hospitalization, mechanical ventilation, and mortality of patients with COVID-19 infection., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)