To investigate the effectiveness of the combination of thiamine, ascorbic acid, and hydrocortisone (triple therapy) as an adjuvant therapy to the routine protocol of managing sepsis in the critical care setting. A prospective randomized comparative study done in the intensive care unit of medical city teaching hospital. Fifty patients with the diagnostic criteria of sepsis who needed admission to the intensive care unit has been studied, twenty-five of them (group A) received the combination: Vit. C, Thiamine, Hydrocortisone for five days with daily monitoring of patients’ clinical and laboratory status to study the effectiveness of this combination as an adjuvant therapy to the standard management of sepsis in the intensive care unit while the other group; the control group (group B) received only the standard management of sepsis. The mortality rate in the study group (group A) was only 20% (5 patients) after 5 days of triple therapy in addition to the conventional treatment of sepsis, while it is 48% (12 patients) for the control group (group B) who did not receive the combination in this study. The combination therapy of vitamin C, thiamin and Hydrocortisone is effective as an adjunctive therapy to the principal line of management of sepsis.