Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2 . Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics . When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease . Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity . Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials . Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals . Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.