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To investigate the relationships between serum adipocytokines, body mass index (BMI), disease activity, and symptoms of depression and anxiety in patients with axial spondyloarthritis (axSpA). Ninety-three patients with axSpA and 100 age- and sex-matched healthy controls were assessed. Serum adipocytokines (resistin, leptin, fetuin-A, visfatin) and ghrelin, BMI, and disease activity (BASDAI, ASDAS-CRP) were measured. Depression and anxiety were evaluated using the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Patients with axSpA exhibited higher BDI-II (6.76 ± 6.81 vs 2.81 ± 3.31, p < 0.001) and BAI scores (6.67 ± 7.71 vs 3.89 ± 3.88, p < 0.05) than controls, with the somatic domain most pronounced. Depressive and anxiety symptoms correlated strongly with disease activity (ASDAS-CRP and BASDAI) but not with BMI or spinal involvement. Leptin and ghrelin reflected BMI, whereas fetuin-A and resistin were independently associated with affective symptoms: doubling of fetuin-A increased BDI-II and BAI scores by ~ 4 and 3 points, respectively, whereas doubling of resistin decreased them by ~ 2.5 points. Resistin was inversely correlated with BASDAI (r = -0.33, p < 0.05) and anxiety (r = -0.42, p < 0.001). Other adipocytokines showed limited associations with clinical or psychological measures. Depressive and anxiety symptoms in axSpA are primarily driven by inflammatory burden rather than BMI or structural disease severity. Fetuin-A and resistin exert opposing effects on affective symptoms, highlighting disease-specific immunometabolic pathways. Early identification of psychological distress and integrated management with anti-inflammatory therapy are warranted.