Objectives: This study aimed to evaluate the antiviral efficacy of lopinavir/ritonavir alone or combined with arbidol in the treatment of hospitalized patients with common coronavirus disease-19 (COVID-19). Methods: In this retrospective observational study, COVID-19 hospitalized patients were identified and divided into two groups based on the antiviral agents used during their hospitalization. Group-LR patients were treated with single antiviral drug of lopinavir-ritonavir. Group-LR+Ar patients were treated with lopinavir-ritonavir combined with arbidol for antiviral therapy at least 3 days. Patients were assessed for different clinical outcomes. Results: A total of 34 and 39 patients were identified for Group-LR and Group-LR+Ar, respectively. Treatment with lopinavir-ritonavir alone was not difference from lopinavir-ritonavir combined with arbidol in overall cure rate of COVID-19 hospitalized patients (92.3% and 97.1%, respectively). In a modified intention-to-treat analysis, lopinavir-ritonavir combined with abidol led to a median time of hospital stay that was shorter by 1.5 days than group-LR (12.5 days vs. 14 days). The percentages of COVID-19 RNA clearance was 92.3 in group-LR and 97.1 in group-LR+Ar. The mean time of virus turning negative was 11.5 plus-or-minus sign 9.0 days in group-LR+Ar that were longer than group-LR. Treatment of lopinavir-ritonavir combined with arbidol did not significantly accelerate main symptoms improvement and promote the image absorption of pulmonary inflammation. Conclusion: No benefit was observed in the anti-virus effect of lopinavir-ritonavir combined with arbidol compared with lopinavir-ritonavir alone in the hospitalized patients with COVID-19. More clinical observations in COVID-19 patients may help to confirm or exclude the effect of antiviral agents.