BACKGROUND: The release of pro-inflammatory cytokines, resulting in cytokine storm syndrome, contributes to the morbidity and mortality associated with COVID-19 disease. This study aimed to compare the effects of intravenous (IV) and subcutaneous (SC) tocilizumab, an IL-6 receptor antagonist, on respiratory parameters and clinical outcome in patients with COVID 19. METHODS: We performed a retrospective cohort study of hospitalized patients with COVID-19 treated with either IV or SC tocilizumab from March 26, 2020, to May 18, 2020. Respiratory parameters seven days after receiving tocilizumab therapy were compared to baseline measurements. All patients were assessed until discharged from the hospital. RESULTS: Tocilizumab was administered to 125 patients: 65 received IV, and 60 received SC therapy. At day seven, 52% of the IV group patients demonstrated improvement in respiratory parameters, compared to 28% in the SC group (P = 0.01). Mortality rates at days seven and 28 were 15% and 37%, respectively, in the IV group and 17% and 50%, respectively, in the SC group (PNS). The in-hospital mortality rate was 38% for the IV group versus 57% for the SC group (P = 0.04). More than 90% of patients in each group received corticosteroids; however, significantly more patients received convalescent plasma in the IV group. CONCLUSIONS: At the doses used in this study, IV tocilizumab is preferred over SC therapy to treat cytokine storm syndrome due to COVID-19.