Objective To investigate the effect of intravenous omega-3 fish oil on the prognosis of patients with sepsis. Methods 1733 patients with sepsis were selected from the Department of Critical Care Medicine of Shenzhen People's Hospital from December 1, 2016 to June 30, 2019. According to the survival situation, these patients were divided into survival group(n=1351) and death group (n=382). The general information, infection site, complications, organ support measures and clinical outcomes were analyzed and compared between the two groups. Multivariate logistic regression and Kaplan-Meier survival analysis were performed to evaluate the effect of intravenous supplementation of omega-3 fish oil on the prognosis of patients with sepsis. Results There were significant differences in gender, age, pulmonary infection, abdominal infection, blood infection,complication, mechanical ventilation, renal replacement therapy and omega-3 fish oil intervention between survival group and death group (P<0.05). There was no significant difference in the proportion of biliary tract infection, urinary tract infection and other site infections between the two groups (P>0.05). Logistic regression analysis showed that men, old age, bloodstream infection,mechanical ventilation support, and renal replacement therapy were risk factors for the survival status of patients with sepsis within 90 days, and intravenous omega-3 fish oil supplementation was a protective factor for sepsis. Survival analysis results show that intravenous supplementation of omega-3 fish oil can improve the 90-day survival rate of patients with sepsis. Conclusion Omega-3 fish oil intervention can improve the prognosis of patients with sepsis, and the clinical application feasibility is high.