Objective We assessed the association of suPAR (soluble urokinase plasminogen activator receptor) plasma levels with fibrotic and vascular manifestations in patients with systemic sclerosis (SSc). Methods suPAR plasma levels were measured in 121 consecutive patients with SSc and correlated to pulmonary and vascular features of SSc, including interstitial lung disease as characterized by percentage of predicted CO diffusing capacity (DLco) and forced vital capacity (FVC), pulmonary fibrosis by computed tomography, and pulmonary arterial hypertension, telangiectasias, and digital ulcers. Results Overall, 121 SSc patients (84% females; mean age, 57 ± 12 [range: 22-79] years) were enrolled; 35% had diffuse cutaneous SSc. suPAR plasma levels ranged from 1.3-10.2 [median: 2.9 (p25-p75: 2.3-3.9)] ng/mL. Log(suPAR) levels correlated with DLco (r = -0.41, p 2.5 ng/mL showed a sensitivity of 91% for identifying patients with either DLco Conclusion suPAR levels strongly correlated with pulmonary involvement in SSc. Future studies should test if suPAR estimation can be used for surveillance of severe pulmonary involvement in SSc.