Abstract： Objective::Vitiligo is a relatively common skin disfiguring disorder that exhibits a fluctuating course between activity and stability, making monitoring and management challenging. Autoimmunity plays a crucial role in the pathogenesis of vitiligo. Numerous autoimmune disorders have been associated with both CD27 and chemokine (C-X-C motif) ligand 10 (CXCL10). However, trials evaluating their role in vitiligo are lacking in the Egyptian setting. We evaluated the circulating levels of these 2 biomarkers in patients with vitiligo and the possible correlation between their levels and disease activity.Methods::This cross-sectional study included 70 patients with vitiligo and 20 healthy controls. The patients were clinically assessed and then divided into active and stable groups according to clinical signs of activity and Vitiligo Disease Activity scores. The levels of CD27 and CXCL10 in the serum were assessed using an enzyme-linked immunosorbent assay in both the patients and the controls, then the Mann-Whitney U and Kruskal-Wallis tests were used to analyze the difference between the groups. Results::Active and stable vitiligo patients have significantly higher median serum CXCL10 (385.9 and 245.2 pg/mL) and CD27 (61.6 and 66.5 ng/mL) levels compared to the controls (193 pg/mL and 52.5 ng/mL, respectively, all P < 0.05). In vitiligo cases, although CXCL10 levels significantly increased with disease activity ( P < 0.001), CD27 levels were comparable between the 2 subgroups ( P = 0.953). CXCL10 positively correlated with disease activity ( r = 0.887, P < 0.001). CXCL10 had a higher sensitivity and a lower specificity (95.7% and 60.0%, respectively) compared to CD27 (71.4% and 75%, respectively) for differentiating cases from controls. Conclusion::There is a possibility that CXCL10 and CD27 are involved in the development and course of vitiligo.