Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with increased cardiometabolic risk. Adipokines are implicated in inflammation and metabolic dysregulation in RA; however, clinical data on serum asprosin, a novel glucogenic adipokine, remain limited. This study aimed to evaluate serum asprosin levels in patients with RA and to assess their relationship with disease activity. In this single-center, cross-sectional observational study conducted between June and August 2025, 42 patients with RA and 40 control participants were included. Serum asprosin levels were measured using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using the Disease Activity Score in 28 joints, based on the erythrocyte sedimentation rate (DAS28-ESR). Associations between asprosin levels and clinical, laboratory, and serological parameters were analyzed. Serum asprosin levels differed significantly between patients with RA and control participants, with median (interquartile range) values of 12.43 (9.98) and 9.96 (3.47) ng/mL, respectively ( P = .025); however, this association was no longer statistically significant after adjustment for age, sex, BMI, smoking status, and comorbidity in a multivariable regression model (adjusted P = .986). No significant correlations were observed between asprosin and DAS28-ESR, CRP, ESR, RF, or anti-CCP. ROC analysis demonstrated limited discriminatory performance (AUC = 0.643; 95% CI: 0.52–0.767; P = .02). Serum asprosin levels differed between patients with RA and control participants in unadjusted analysis; however, this difference was not retained after adjustment for potential confounders, and no significant association with disease activity or inflammatory markers was identified. These findings suggest that serum asprosin may have limited clinical utility as a standalone biomarker in RA. Further prospective studies with larger sample sizes are needed to clarify the potential role of asprosin in RA pathophysiology.