Systemic sclerosis "SSc" is an autoimmune multiple system connective tissue disorder characterized by impairment of the microvasculature and fibrosis of skin and internal organs. The study aimed to assess serum interleukin 6 (IL-6) as a potential biomarker of SSc in association with clinical presentation and laboratory investigations in Egyptian SSc patients. Twenty-seven SSc cases diagnosed according to "the 2013 American College of Rheumatology/European League Submit Date Revise Date 2020-12-20 2021-01-13 Against Rheumatism" (ACR/EULAR) and controls were enrolled in this study. For all participants, detailed history was undertaken, and clinical examination and laboratory investigations were performed. In addition, serum IL-6 was evaluated using Enzyme-Linked Immunosorbent Assay (ELISA) technique. Serum IL-6 level was significantly higher in cases than controls (14.7±8.9 ng/L VS 6.7±3.5 ng/L respectively) (p-value=0.0001). The receiver operator characteristics (ROC) curve showed the best cutoff value for serum IL-6 in SSc patients to be 8.9 ng/L, with a sensitivity of 92%, specificity 78%, accuracy 85% and CI 95% (0.87-1.0) (AUC=0.94). It was significantly higher among SSc cases with Interstitial Lung Disease (ILD) than those without ILD and among patients with skin fibrosis than those without fibrosis (P value=0.02 and 0.03) respectively. Significant positive correlations were found for serum IL-6 level with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (r=0.6 and 0.7 respectively). Serum IL-6 level may be used as a noninvasive predictor of organ involvement and disease progress in SSc. Further researches are needed to assess its possible role in treatment of Egyptian SSc patients.