Objectives The efficacy of omega-3 fatty acids in the treatment of sepsis is controversial. We conducted an updated meta-analysis to clarify the efficacy of omega-3 fatty acids in patients with sepsis. Methods PubMed, EMBASE, and the Cochrane Library were searched for randomized clinical trials (RCTs) on omega-3 fatty acid supplementation in adults with sepsis. Results Twenty eligible RCTs involving 1514 patients were included in the meta-analysis. Omega-3 fatty acid supplementation was linked to reductions of mortality ( I2 = 0, relative risk [RR] = 0.82, 95% confidence interval [CI] = 0.69–0.97), the duration of mechanical ventilation (DMV; I2 = 74%, weighted mean difference [WMD] = −2.20, 95% CI = −4.00 to −0.40), and intensive care unit (ICU) length of stay (LOS; I2 = 91%, WMD = −3.86, 95% CI = −5.72 to −2.01). Subgroup analysis illustrated that mortality was significantly reduced in patients with sepsis and gastrointestinal dysfunction (RR = 0.5, 95% CI = 0.29–0.86, I2 = 0). Conclusion Omega-3 fatty acid supplementation might be associated with reduced mortality in patients with sepsis, especially those with gastrointestinal dysfunction. Furthermore, omega-3 fatty acid administration could shorten DMV and ICU LOS.