Abstract Background Although more than a year past since COVID-19 was defined, there is no specific treatment yet. Since COVID-19 management differs over time, it is hard to determine which therapy is more efficacious. In this study, we aimed to evaluate the efficacy of the regimen with Favipiravir (FPV) and determine if the timing of FPV addition offers any improvement. Methods A retrospective observational case-controlled cohort study was performed between March and September 2020, including adults with COVID-19 in a single-center in Turkey. We categorized patients into age-sex matched three groups, group 1 (n = 48) and group 2 (n = 48) included patients treated with the combination of FPV plus Hydroxychloroquine (HQ) early and late, respectively. Group 3 (n = 48) consisted of patients on HQ monotherapy. In Group 2, if the respiratory or clinic condition had not improved sufficiently, FPV was added on or after day 3. Results We found that starting FPV early had an impact on PCR negativity and the progression of the disease. 'No progression' was defined as the absence of a new finding in the control radiological examination and the absence of accompanying clinical deterioration. Also, the decrease in C-reactive protein (CRP) was greater in Group 1 than Group 3 (p < 0.001). However, we found that early initiation of FPV treatment did not have a positive effect on the estimated survival time. Conclusions According to this retrospective study results, we believe that for better clinical outcomes, FPV treatment should be started promptly to enhance antiviral effects and improve clinical outcomes.