This prospective observational study describes the pharmacokinetic characteristics of favipiravir in adult patients hospitalized for mild to moderate COVID‐19 with a positive RT‐PCR test. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a maintenance dose of 1200 mg/day. Serial blood samples were collected on Day 2 and Day 4 of the therapy. Laboratory findings of the patients (n = 21) and in‐hospital mortality were recorded. Favipiravir concentrations exhibited substantial variability and a significant decrease during the treatment of COVID‐19. The median favipiravir trough concentration (C0‐trough) on Day 2 was 21.26 (interquartile range [IQR], 8.37–30.78) μg/mL, whereas it decreased significantly to 1.61 (IQR, 0.00–6.41) μg/mL on Day 4, the area under the concentration–time curve decreased by 68.5%. Day 2 C0‐trough of female patients was higher than male patients. Our findings indicate that favipiravir concentrations show significant variability during the treatment of COVID‐19 and therapeutic drug monitoring may be necessary to maintain targeted concentrations. [ABSTRACT FROM AUTHOR]