In this study, we assess population-level data of COVID-19 treatments in Iran compared to Ministry of Health (MOH)-published guidelines to gain a better insight into the quality of care for this disease. Methods: National sales data of each recommended and nonrecommended COVID-19 medicine were used to proxy utilization between March 21, 2020, and March 21, 2021, or Iranian year 1399. COVID-19–attributed sales volume and number of patients were estimated by adjusting sales data with pre-COVID-19 average growth rate, recommended dose, and duration of treatment. Next, they were compared with the MOH guidelines in outpatient and inpatient settings. Furthermore, the list of top 10 molecules of the market and top 10 COVID-19–indicated molecules in terms of values were extracted to assess the economic burden of COVID-19 prescription drugs and their share. Findings: The estimated number of patients receiving COVID-19 treatments in some outpatient medicines such as recommended hydroxychloroquine was over 2.2 million. Favipiravir and remdesivir were collectively about two inpatient medicines 260,000; however, neither of these two medicines was recommended in the MOH guidelines. In some fewer specific medicines such as dexamethasone, prednisolone, azithromycin, and naproxen, the estimated number of COVID-19–attributed patients were incomparable with the officially announced number of confirmed cases in the year of study, which could be related to nonconfirmed diagnosed cases, irrational use, or prescribing, or limitations of our data and study. The total COVID-19–attributed market of candidate medicines was over 15 trillion IR Rials (almost 4.3% of the total market). Remdesivir, with over 60% of the total COVID-19 attributed market, followed by favipiravir, was among the highest value medicines. Conclusion: Despite the release of the COVID-19 guideline by Iran MOH, misalignment in the enforcement of decisions was a serious weakness (cases of favipiravir and remdesivir). This weakness led to some economic burden on the health-care system and raised ethical concerns.