Objective: The aim of this study is to evaluate and compare the clinical efficacy of lopinavir/ritonavir with oseltamivir plus hydroxychloroquine for the treatment of Covid-19, in order to find a better treatment for Covid-19 patients. Methods: In this single-center, mixed designed cohort study, 198 patients admitted for Covid-19, to Ziaeian Hospital, Tehran, Iran were included. According to the date of admission, the patients were received different treatments and divided into two groups. Group 1 received oseltamivir with hydroxychloroquine and azithromycin whereas group 2 received lopinavir/ritonavir with azithromycin. Patients’ outcomes were measured based on duration of hospitalization, a requirement to intensive care unit (ICU) admission, need for intubation and mortality. Results: Patients in group 1 had greater clinical improvement and shorter duration of hospitalization. Although small in number, mortality, ICU admission, and intubation was also less in this group, but due to the small number of events in incidence of ICU admission, intubation, and mortality, it could not be analyzed and was not possible to investigate the relationship between the type of treatment and these variables. In group 1, one patient was admitted to ICU, while 12 patients were admitted to ICU in group2. None of the patients in group 1 required intubation whereas 4 in group 2 received intubation. One patient in group 1 and 9 patients in group 2 died. Conclusion: This study showed that administration of Oseltamivir plus hydroxychloroquine is likely to be associated with earlier clinical improvement and shorter duration of hospitalization however, further studies are required.