We attempted the cocktail treatment of favipiravir, steroid, and heparin for COVID-19. This study aimed to evaluate the effect of cocktail therapy for severe COVID-19.The treatment protocol was as follows: oral favipiravir (3600 mg on Day 1, 1600 mg from day 2 to day 14), methylprednisolone (1000 mg for 3 days), and low molecular weight (2000 IU every 12 h) or unfractionated heparin (10,000-12,000 IU/day). Thirteen patients with COVID-19 requiring mechanical ventilation were admitted during the study period. Mean patient age was 63 (range, 46-80) years, and 69.0% were men. Only one patient required extracorporeal membrane oxygenation. Time from first symptom appearance to favipiravir administration was 8.7 (range, 4-13) days. The P/F ratio changed very little over the first 6 days and then gradually recovered. The Interleukin-6 peaked on Day 4 and decreased thereafter. Presepsin also peaked on Day 3, remained about the same until Day 6, and then decreased. The clinical course of SARS-CoV-2 treatment with the cocktail in mechanically ventilated patients with COVID-19 indicated that favipiravir could partially control inflammatory mediators but could not completely control them or respiratory status.