OBJECTIVES: Both absolute and restrictive iron deficiency with a highly ferritin level has been observed in COVID-19 patients. Remdesivir and Favipiravir are currently used in the management of COVID-19 without clinical or laboratory evidence that these drugs are potentially harmful to the blood elements. This study aims at the determination of the effect of remdesivir and favipiravir on the red cell indices that discriminate the absolute from restrictive iron deficiency. MATERIALS and METHODS: A total number of 149 COVID-19 patients were included in this cross-sectional study; 70 patients were treated with health care (Group I); 17 patients were treated with remdesivir (Group II); and 62 patients were treated with favipiravir (Group III). Complete blood count, red cell indices, C-reactive protein, and D-dimer were determined as primary outcomes.RESULTS: There are no significant differences in the hematological indices, C-reactive protein, and D-dimer between treated groups. Significant differences between the studied groups who have been observed in the Lal and Shine index, and England and Fraser’s index. The red cell indices of patients treated with remdesivir indicated that the patients have significantly restrictive iron deficiency compared with patients treated with favipiravir. These changes are not related to the d-dimer levels.CONCLUSION: Patients treated with favipiravir showed improvement of the iron utilization by tissues as the percentage of patients who have restrictive iron deficient is lower than the corresponding percentage of absolute iron deficiency compared with patients treated with remdesivir.