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Introduction: the decision to supplement total parenteral nutrition (TPN) with emulsions of omega-3 (O3) eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids (FA) of marine origin is based on the clinical benefits obtained in different medical situations and surgical procedures, among which reductions in hospital stay, days of mechanical ventilation, incidence of infections and mortality stand out. However, the evidence in critically ill patients remains contradictory. Objective: the objective of this clinical trial was to analyze the effect of supplementation with EPA/DHA O3 FAs on clinical prognostic markers -medical, nutritional and biochemical-in critically ill patients, relating to outcome. Method: a clinical, controlled, randomized, single-center trial in 64 critically ill adult patients, of which 47 patients were randomized to receive TPN supplemented with EPA/DHA O3 FAs in doses of 0.1 g/kg/day (n = 23) and 0.2 g/kg/day (n = 24), compared with a historical control group with TPN without supplementation (n = 17). Clinical prognosis markers were determined at baseline and at the end of nutritional support (medical, nutritional and biochemical). Results: the two groups with supplementation showed a statistically significant reduction in mortality (p < 0.005); the clinical prognostic markers SOFA, APACHE II, SAPS 3, NUTRIC, RTL and CRS were consistent in showing a significant improvement (p < 0.005), of prognosis with doses of 0.1 and 0.2 g/kg/day of EPA/DHA O3 FAs, respectively. Conclusion: supplementation of parenteral nutrition with EPA/DHA O3 fatty acids at doses of 0.1 g and 0.2 g/kg/day improves recovery prognosis and the probability of survival in critically ill patients. [ABSTRACT FROM AUTHOR]