Abstract Background/purpose Elevated levels of C-reactive protein (CRP) in systemic sclerosis (SSc) have been linked to early inflammatory stages of the disease. This study has been designed to investigate CRP levels longitudinally in a cohort of SSc patients and to correlate these findings with comorbidities and disease characteristics. Methods In this retrospective study, patients with SSc treated at the outpatient clinic of the Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, were analyzed. Only patients with at least three consecutive visits and at least 1 year follow-up were included in this study. CRP serum levels were measured at every visit and categorized as positive if CRP concentrations were ≥ 5 mg/l. Subjects with elevated CRP levels at more than 80% of visits were defined as inflammatory SSc. The longitudinal CRP profiles were correlated with disease characteristics and comorbidities. Results A total of 1815 consecutive visits of 131 SSc patients were analyzed. Over the observed time span (7.6 (1.0–19.5) years), 18.3% (n = 24) of patients had continuously elevated CRP levels (inflammatory SSc), whereas in 29% (n = 38), CRP levels were always in the normal range. There was no association between disease duration and CRP levels at first visit. Inflammatory SSc was associated with male gender (p = 0.022), anti-Scl-70 antibodies (p = 0.009), diffuse cutaneous SSc (p = 0.036), pulmonary fibrosis (p
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