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Background and Objectives: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers., Patients and Methods: Observational case-control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls., Results: A total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p<0.001), but no higher CXCL4 or CXCL8 levels. GDF15 was associated with Diffuse SSc, pulmonary arterial hypertension, interstitial lung disease, less forced vital capacity, high titles of antiScl70, disease activity, and dilated loops in capillaroscopy. CXCL4 levels were associated to a higher Rodnan punctuation, while CXCL8 was associated to C4 fraction consumption and tortuosities in capillaroscopy., Conclusions: GDF15 high levels were associated with diffuse SSc, lung impairment, disease activity and changes in capillaroscopy. Moreover, CXCL4 was only associated with skin impairment, while CXCL8 was not related to organic damage., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)