Aim: Current study designed to identify whether the combination of vitamin C, hydrocortisone, and thiamine, to decrease the mortality and free of vasopressor administration in patients with septic shock. Method: An open-label, randomized Quasi experimental study conducted in 240 cases of sepsis at intensive care unit for the duration of 3 years. Standard care group consists 120 and Interventional consists 120 (Standard care with Hydrocortisone, Vitamin C, and Thiamine). The primary endpoint hospital survival and secondary outcome the duration of vasopressor therapy and other outcomes were measured. Result: Among 240 patients who were randomized, the primary outcome measurement recorded as 3cases (1.25%) in Interventional and 31cases (12.91%) in Standard groups. All patients in the interventional group were weaned off vasopressors with a mean of 17.5±10.2 hrs after starting treatment with the vitaminC+thiamine+hydrocortisone infusion. The mean duration of vasopressor use was 35.8±21.5 h in the standard group (p=0.001); 25% patients in the standard group received higher dose of vasopressors and died due to refractory septic shock. The mean duration of vasopressor treatment is 61.4± 33.8 h in the control patients who died compared with 39.5±12.5h in those who survived. The median length of Hospital stay is 13.64 ± 9.04 (4-80) days in the interventional group compared with 10.28 ± 5.93 (2-28) days in the control group. Conclusion: Early use of intravenous vitamin C, together with hydrocortisone and thiamine, may prove to be effective in the reduction of vasopressors dosage and mortality of patients with sepsis and septic shock.