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Background Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with systemic inflammation and metabolic alterations that may influence circulating lipid profiles. While polyunsaturated fatty acids have been widely studied, less is known about monounsaturated fatty acids (MUFAs), their endogenous synthesis and their relationships with disease activity and adiposity.Methods In this cross-sectional study, 52 individuals with RA and 30 matched controls were recruited (2017–2022). Disease activity (Disease Activity Score in 28 joints-C reactive protein (DAS28-CRP)), body composition and metabolic parameters were assessed. Dietary intake was captured using a 4-day food journal. Plasma fatty acids were measured by gas chromatography and the stearoyl-CoA desaturase-1 (SCD-1) index estimated endogenous MUFA synthesis. Multivariable regression with false discovery rate correction was used.Results Participants with RA had lower insulin sensitivity, higher triglycerides and lower physical activity levels. Plasma oleic and palmitoleic acids and the SCD-1 index were higher in RA, while linoleic and arachidonic acids were lower; saturated and omega-3 fatty acids did not differ. After adjustment for age, sex and diet, oleic acid was associated with RA status (β=1.4; 95% CI 0.33 to 2.5) and waist-to-hip ratio (β=14; 95% CI 6.9 to 21). Among participants with RA, higher oleic acid and gondoic acid were associated with DAS28-CRP, while palmitoleic acid was higher in women but not associated with DAS28-CRP.Conclusions Circulating MUFAs are associated with RA status, adiposity and disease activity after adjusting for diet, supporting a role for endogenous lipid metabolism in RA.