Background: Several studies have investigated the effect of omega-3 fatty acids and vitamin E on oxidative stress and inflammation, but their findings are inconsistent. The aim of this meta-analysis is to elucidate the overall effects of co-supplementation with omega-3 fatty acids and vitamin E on oxidative stress and inflammation. Methods: We searched titles, abstracts, and keywords of relevant articles indexed in PubMed, ISI, Scopus, and Google Scholar databases up to December 2018 to identify eligible RCT studies. Random effects model was used to estimate the pooled effect of co-supplementation with omega-3 fatty acids and vitamin E on oxidative stress and inflammation. Results: Overall, 7 RCTs with 504 participants were included in this meta-analysis. We found that co-supplementation with omega-3 fatty acids and vitamin E decreased hs-CRP (weighed mean difference (WMD) = -2.15 mg/L; 95% CI: -3.40, -0.91 mg/L; P < 0.001) concentrations and increased total antioxidant capacity (TAC) (WMD = 92.87 mmol/L; 95% CI: 31.97, 153.77 mmol/L; P = 0.03), and nitric oxide levels (NO) (WMD: 6.95 μmol/L; 95% CI: 3.86, 10.04, P < 0.001) compared with control group. Omega-3 fatty acids and vitamin E had no significant effect on malondialdehyde (MDA) (WMD: 1.54 mmol/L; 95% CI: -1.29, 4.36; P = 0.196), and glutathione (GSH) (WMD: 20.87 mmol/L; 95% CI: -20.04, 61.6, P = 0.31) levels. Conclusion: The present meta-analysis found that omega-3 fatty acids and vitamin E co-supplementation significantly decreased hs-CRP and increased NO and TAC, although it had no significant effect on MDA and GSH.