Purpose: Chronic spontaneous urticaria (CSU) is a disease that is primarily seen in adults and is comparatively rare in children. Consequently, only a few studies have focused on the pathogenesis of the disease in children. This study investigated the possible role of metalloproteinase-9 (MMP-9) in the pathogenesis of CSU in children. Methods: The study group was composed of 54 children with CSU; 34 healthy children comprised the control group. The demographic and clinical features of the study group were extensively evaluated, and laboratory assessments were also performed. An enzyme-linked immunosorbent assay was used to evaluate levels of plasma MMP-9. Disease activity was quantified using the urticaria activity score (UAS). Results: The median value of plasma MMP-9 was 108.9 ng/mL (interquartile range, 93.3-124.1) in the CSU group and 87.8 ng/mL (69.4103.0) in the control group. The difference between the 2 groups was statistically significant (P<0.001). Also, MMP-9 levels showed a significant positive correlation with UAS (rho=0.57, P<0.001). Twenty-six percent of patients had positive autologous serum skin test (ASST) results. Neither UAS nor plasma MMP-9 levels were significantly different between ASST-positive and -negative patients (P>0.05). Conclusions: Plasma MMP-9 levels were elevated in children with CSU and were positively correlated with disease activity. MMP-9 may be both a good biomarker of disease activity and a potential therapeutic target in CSU.