Total antioxidant capacity (TAC) in severe septic patients has been analyzed in few studies with limited number of subjects. In addition, no association between TAC serum levels and mortality in patients with sepsis has been investigated. We aimed at assessing a possible relationship between TAC serum levels and mortality using a large cohort of patients with severe sepsis. We performed an observational, prospective, multicenter study in 6 Spanish intensive care units. Serum levels of TAC were measured in a total of 213 patients with severe sepsis. End point was 30-day mortality. Nonsurviving septic patients (n = 75) showed higher serum TAC levels (P = .006) than survivors (n = 138). Cox regression analysis showed that TAC serum levels were associated with 30-day survival (hazard ratio = 1.50, 95% confidence interval = 1.16-1.94, P = .002). Receiver operating characteristic analysis showed that the area under curve of TAC serum levels to predict 30-day survival was 0.61 (95% confidence interval = 0.545-0.680, P = .04). The most relevant and new findings of our study, the largest cohort of septic patients providing data on circulating TAC levels so far, were that serum TAC levels are associated with mortality and could be used as biomarker to outcome prediction in severe septic patients.