PURPOSE: Omega-3 fatty acid is an emerging hotspot on anti-inflammation and chronic obstructive pulmonary disease (COPD) is known as a chronic inflammatory disease. The effect of Omega-3 fatty acid supplement on patients with COPD remains mixed for insufficient evidence. This systematic review and meta-analysis is based on neat randomized controlled trials trying to give a clearer impression on the effect of Omega-3 on patients with COPD. METHODS: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. Randomized clinical trials (RCTs) published in electronic databases including Medline, Embase, Cochrane Library, ClinicalTrials.gov and China National Knowledge Infrastructure (CNKI) by May 10, 2021 were searched. Data extracted from 6 predetermined domains (nutritional condition, lipid composition, inflammatory biomarker, lung function, physical endurance and quality of life [QoL]) were reviewed and analyzed. RESULTS: A total of 8 RCTs evaluating 418 patients (age, mean [SD] = 67.3 [10.2] years) were included. Statistical differences were found in 3 parameters of 3 domains - weight (Wt) (0.25 [95% CI, 0.02 to 0.48], P = 0.03) in nutritional condition, low-density lipoprotein (LDL) (0.70 [95% CI, 0.30 to 1.10], P = 0.00) in lipid composition and interleukin-6 (IL-6) level (-0.32 [95% CI, -0.60 to -0.05], P = 0.02) in inflammatory biomarker - while no significant difference was found in lung function, physical endurance or QoL. CONCLUSION: Comparing with placebo, Omega-3 intake was associated with more weight-gaining, LDL increase and IL-6 reduction. These results should be interpreted cautiously for the quality and quantity of available evidence are limited.