Abstract Background SARS-CoV-2 was identified as a worldwide fatal pandemic that causes acute respiratory infections. The aim of this work was to compare the effect of Using combined therapy: (tocilizumab with Methylprednisolone) versus using (Methylprednisolone alone) as immuno-modulatory therapy on 28 days mortality mortality, need for mechanical ventilation & adverse effects. Methods This retrospective observational cohort study was carried out on 60 patients diagnosed as having covid 19 infection with cytokine storm and severe acute respiratory syndrome during the period(2020-2021). Patients were divided into 2 groups: (TCZ+MP)group received 2 doses of tocilizumab within 24 hrs (5 mg/kg in each dose) in addition to a dose of methylprednisolone(2mg/kg/day)for7days and(MP)group:received only a dose of methylprednisolone (2 mg\kg\day) for 7days. All patients were subjected to routine laboratory investigations (Complete blood count, liver function tests, kidney function tests, LDH, ferritin, D-dimer, frequent ABGs (P/F ratio), CRP, IL6, procalcitonin& albumin), and radiology investigation (Chest x-ray and CT chest). Results 60 patients with ARDS(both genders) were included in this study, in TCZ+MPgroup, 8(26.67%) of 30 patients died, compared to 17(56,67%) of 30patients in (MP)group, so mortality rate was significantly lower in patients on TCZ+MPgroup than those on (MP)group (P value =0.018). In TCZ+MPgroup, 12(40%) of 30 patients needed mechanical ventilation compared to 22(73.33%) of 30 patients in MP group, so Number of patients who required mechanical ventilation was significantly lower in patients on TCZ+MPgroup than MP group (P value = 0.009). Adverse effects of intervention drugs after 28 days were insignificantly different between both groups (P value = 0.018). Conclusions In patients with severe COVID-19 infection, combination therapy of tocilizumab &methylprednisolone reduced mortality rate and need for mechanical ventilation as compared with the use of methylprednisolone alone.