Objective To systematically review the efficacy of enteral nutrition with eicosapentaenoic acid ( EPA) , gamma-linolenicacid ( GLA) , and anti-oxidants for patients with sepsis. Methods We searched the PubMed, EMbase, Cochrane Library, Wanfang Database, CNKI and VIP for all randomized controlled trials about the efficacy of an enteral diet enriched with EPA, GLA, and anti-oxidants for patients with sepsis. The quality of the studies was evaluated by the method recommended by Cochrane Collaboration. Meta-analysis was conducted using the Cochrane Collaboration’s RevMan 5.0 software.Results Three RCTs involving 350 patients were included in our systematic review. The results showed a significant reduction in the length of ICU stay ( MD =6.21, 95% CI: 4.61-8.19; P lt;0.00001) and hospital stay ( P lt;0.0001) , a fewer development of neworgan dysfunctions in the patients fed with the study diet and no more adverse events were observed. However, no significant difference in 28-day mortality of all cause was revealed( RR=0.83, 95% CI: 0.60-1.16, P = 0.27) . There were controversial results about the duration of mechanical ventilation.Conclusion A diet enriched with EPA, GLA, and elevated antioxidants is safe and beneficial for the clinical outcome in patients with sepsis.