Fluvoxamine is a selective-serotonin reuptake inhibitor (SSRI), well-tolerated and widely available, usually used in the management of mental-health conditions. Fluvoxamine is also a sigma-1 agonist with high affinity to this receptor and this pharmacodynamical effect has been being portrayed as the main explanation in emerging evidence about the potential of using fluvoxamine in COVID-19 patients. This systematic review was conducted according to the PRISMA guidelines. The search was run in MEDLINE, Web of Science, and CENTRAL from the Cochrane databases. The study protocol was registered in PROSPERO (CRD42022302025). Our aim was to assess the present evidence for therapeutic role of fluvoxamine in COVID-19 patients, the review included studies which evaluate the effect of fluvoxamine in COVID-19 patients. The main outcomes evaluated in the review were: mortality, need for hospitalization (outpatients) and clinical deterioration. The quality control of the selected articles was made using Cochrane’s Risk of Bias tool for the randomized controlled trials (RCTs) and the ROBINS-I criteria for non-randomized studies. A total of 4 studies were included in the final qualitative analysis of the review, 2 of which were RCTs, and the others were open-label prospective cohorts. 3 studies assessed outpatient population and 1 evaluated ICU population. Overall, the 4 studies included a total of 1864 participants. In conclusion, 3 studies with outpatients showed that fluvoxamine treatment can prevent clinical deterioration, hospitalisation, or proxy-hospitalisation. The only study with patients hospitalized in the ICU also demonstrated a therapeutic benefit reducing overall mortality.