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Recently, high\u2010density lipoprotein cholesterol (HDLc) have been evidenced to have anti\u2010inflammatory effects, suggesting a potential link between HDL and SLE that needs to be thoroughly studied. The aim was to explore the association between SLE and HDLc through a systematic review with meta\u2010analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review with meta\u2010analysis was conducted to assess mean differences in HDL levels between patients with SLE and healthy controls. Both qualitative and quantitative syntheses were performed, including an assessment of heterogeneity using <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>, a publication bias evaluation, a methodologic quality assessment, and a forest plot under a random effects model. Subgroup analyses were conducted based on disease activity and the report of corticosteroid dosage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 53 studies were included in the qualitative synthesis, and 35 studies were included in the quantitative synthesis, comprising 3,002 patients with SLE and 2,123 healthy controls. Mean HDL levels were found to be lower in patients with SLE as follows: in the meta\u2010analysis including all articles \u22126.55 (95% confidence interval [CI] \u22128.77 to \u22124.33); in patients with mild disease activity \u22125.46 (95% CI \u22128.26 to \u22122.65); in patients with moderate or severe disease activity \u22129.42 (95% CI \u221215.49 to \u22123.34); in patients using corticosteroids \u22125.32 (95% CI \u221210.35 to \u22120.29); and in studies with excellent methodologic quality \u22128.71 (95% CI \u221212.38 to \u22125.03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HDL levels appear to be quantitatively altered in patients with SLE, suggesting a potential contribution to immune dysregulation, highlighting the importance of HDL in autoimmune 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