Background: Although various biomarkers exist for chronic spontaneous urticaria (CSU), their use is limited, particularly in children. Periostin is produced by dermal cells during skin barrier damage and allergic inflammation. Methods: This cross-sectional study aimed to compare serum periostin levels (SPL) between children with CSU and age- and sex-matched healthy controls (HC). The secondary objective was to investigate the association between SPL and disease severity using the Urticaria Activity Score-7 (UAS-7) questionnaire. Results: Overall, 84 participants (CSU, 45; HC, 39) were included in the study. There was no significant correlation between SPL and UAS-7 scores of the patients. Patients receiving leukotriene receptor antagonist plus antihistaminic had significantly lower SPL than those receiving antihistaminic only (44.32 ± 20.18 vs. 61.33 ± 18.50; p=0.009). The mean SPL was significantly lower in the patient group than in the control group (56.41 ± 20.32 ng/mL vs. 71.68 ± 20.36 ng/mL; p=0.001; Cohen’s d=0.750) (aOR: 0.964, 95% C.I.: 0.942-0.987, p=0.002). The receiver operating characteristics (ROC) curve of the SPL was determined to be significant ( p = 0.001), and the area under curve (AUC) of the ROC curve was 0.705 (95% C.I.: 0.593–0.817). Conclusion: Our study is the first to measure SPL in children with CSU. The results indicated that children with CSU had significantly lower SPL than the healthy controls. Although no correlation was found between UAS-7 and SPL, those on more advanced treatments showed significantly lower SPL. Hence, SPL may serve as a promising biomarker for diagnosing and monitoring CSU in children.