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ABSTRACT Objective Behçet's disease (BD) is a chronic multisystem vasculitis characterized by endothelial dysfunction and vascular inflammation. Asprosin is a recently identified adipokine implicated in endothelial injury and proinflammatory signaling. This study aimed to investigate serum asprosin concentrations in patients with BD and their relationship with disease activity and major clinical manifestations. Methods This cross‐sectional case–control study enrolled 49 patients who fulfilled the International Criteria for Behçet's Disease and 48 healthy controls. Disease activity was stratified as mild, moderate, or severe based on organ involvement using Yosipovitch's Behçet's Disease Classification. Serum asprosin levels were quantified using an enzyme‐linked immunosorbent assay. Associations among asprosin levels, disease activity, clinical manifestations, and inflammatory markers were analyzed. Results Serum asprosin concentrations were markedly elevated in individuals with Behçet's disease relative to healthy controls [12.18 (8.27–16.76) vs. 6.12 (4.76–8.61) ng/mL, p < 0.001] and increased incrementally as disease activity intensified ( p < 0.001). Patients with vascular involvement and uveitis demonstrated markedly elevated asprosin levels compared to patients without these manifestations ( p < 0.01). Correlation analysis revealed a strong positive association between serum asprosin levels and disease activity ( r = 0.821, p < 0.001), and a moderate correlation with C‐reactive protein (CRP) levels ( r = 0.431, p = 0.002). In multivariate analysis, both disease activity and CRP levels were independently associated with serum asprosin concentrations. Conclusion Serum asprosin levels are elevated in BD and closely associated with disease activity, systemic inflammation, and major organ involvement, particularly vascular manifestations and uveitis. Asprosin may represent a potential biomarker of the inflammatory and vascular burden in BD.