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This study aimed to identify markers in patients with SSc that are associated with ILD progression. In total, 52 SSc patients and five healthy volunteers (HVs) were included. Patient plasma samples were available for measurement of soluble mediators by metabolomics, proteomics, and cytokine quantification. Gene expression profiling was performed on patients' whole blood and skin biopsies, and immunophenotyping was carried out on peripheral blood mononuclear cells. Comparisons were made between patients with progressive ILD, those with no ILD, and HVs. Our results confirm the involvement of pro\u2010inflammatory mechanisms in SSc\u2010related ILD, with elevated type 1 interferon (IFN1), fractalkine (CX3CL1), and C\u2010C motif chemokine 2 (CCL2), as well as the profibrotic markers C\u2010X\u2010C motif chemokine 17 (CXCL17), thrombospondin (THBS), and latent transforming growth factor beta\u2010binding protein 1 (LTBP1). 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