In sepsis, the antioxidant effects of vitamin C therapy4 may mitigate tissue injury induced by oxidative stress.5 Vitamin C cannot be synthe-sized by humans, and levels are low in many critically ill patients, which has increased the plausibility of benefit with supplementation.6 Af-ter a single-center study spurred interest in the use of intravenous vitamin C, administered with hydrocortisone and thiamine,7 subsequent ran-domized, controlled trials evaluating this com-bination treatment did not show benefits.8,9 In contrast, in a randomized, controlled trial, pa-tients with sepsis and acute lung injury who received a higher dose of vitamin C (50 mg per kilogram of body weight every 6 hours) had a lower 28-day risk of death than those who re-ceived placebo.10 However, recent meta-analyses suggest that the overall evidence supporting the use of vitamin C therapy in patients with sepsis is of low certainty.8,11 In the phase 3, multicenter, randomized, controlled Lessening Organ Dysfunction with Vitamin C (LOVIT) trial, we tested the hypoth-esis that a high dose of vitamin C would reduce the risk of death or persistent organ dysfunc-tion at 28 days in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU).