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Higher circulating total antioxidant capacity (TAC) concentrations have been found in non-survivor than in survivor septic patients at moment of sepsis diagnosis. The objectives of this study were to determine whether serum TAC levels during the first week of sepsis are associated with lipid peroxidation, sepsis severity, and sepsis mortality, and whether could be used as a prognostic biomarker.This prospective and observational study with 319 septic patients admitted to Intensive Care Units was carried out in 8 Spanish hospitals. We determined serum concentrations of malondialdehyde (to estimate lipid peroxidation) and TAC at days 1, 4 and 8 of sepsis. Mortality at 30 days was the end-point study.We found that serum TAC concentrations at days 1, 4 and 8 could predict 30-day mortality according to ROC curve analyses (p < 0.001), that were associated with 30-day mortality according to regression analyses (p < 0.001), and that were associated with serum levels of malondialdehyde and SOFA score.The new findings of our study were that serum TAC levels during the first week of sepsis are associated with lipid peroxidation, sepsis severity, and sepsis mortality, and that could be used as a prognostic biomarker.Serum TAC concentrations during the first week of sepsis could be used as biomarker mortality.An association between sepsis mortality and serum TAC levels during the first week exists.An association between serum TAC levels, lipid peroxidation and sepsis severity during the first week exists.