Background: Although there has been great progress in the field of medicine, mortality associated with the age-old problem of sepsis still remains high. One of the newer modalities to treat sepsis is the hydrocortisone, ascorbic acid (AA), and thiamine (HAT) therapy, using HAT, which is proposed to reduce organ failure and mortality by restoring dysregulated host immune response and mitochondrial function as well as neutralizing reactive oxygen species (ROS). Studies evaluating the treatment of severe sepsis, burns, and trauma with vitamin C administration have shown inconsistent results. Several studies have also shown the detrimental effect of a positive fluid balance on patients with sepsis, including an increased risk of mortality. This study aims to evaluate the effect of vitamin C with thiamine on improving the outcome of septic shock. Materials and methods: This prospective cohort study was conducted at a tertiary care intensive care unit (ICU) and enrolled adult septic shock patients admitted over a 6-month period between April and September 2018. They formed an intervention group that received intravenous (IV) vitamin C 1.5 gm every 6 hours and thiamine 200 mg every 12 hours in addition to antibiotics. This was compared with a retrospective cohort of patients admitted between July to December 2017, which received only antibiotics. Both vitamin C and thiamine were initiated within 6 hours of admission and given for a period of 4 days. Hydrocortisone, as an infusion of 200 mg over 24 hours, was used in all patients on vasopressor support. The primary outcome evaluated was ICU mortality and secondary outcomes, ICU length of stay (LOS), hospital LOS, mechanical ventilation-free days (MVFDs), vasopressor-free days (VFDs), and cumulative fluid balance after 4 days. Results: A total of 30 patients fulfilled the inclusion criteria and formed the intervention group. This was compared with a retrospective group which was equally matched in their baseline characteristics and acute physiology and chronic health evaluation (APACHE) II scores (20 vs 21), as well as antibiotics, are given. ICU mortality was 19% in the intervention group and 34.1% in the retrospective group (p = 0.115). ICU LOS was higher in the intervention group (5 vs 4 days, p = 0.014). There was no difference in the other secondary outcome parameters, namely, hospital LOS (10 vs 8 days, p = 0.141), MVFDs (5 vs 6, p = 0.493), VFDs (4 vs 6, p = 0.415), and cumulative fluid balance (+583 mL vs +450 mL, p = 0.209). Conclusion: Intravenous (IV) administration of vitamin C and thiamine may not be beneficial in improving the outcome in patients with septic shock.