Objective: Eosinophil-derived neurotoxin (EDN) is associated with recurrent wheezing episodes after bronchiolitis, childhood asthma, and allergic rhinitis. We investigated if there is a measurable difference between serum EDN levels in children with wheezing and non-wheezing respiratory infections.Methods: 171 children who visited a university hospital with respiratory infections were enrolled in the study. Subjects were divided into two groups: wheezing (n = 46) and non-wheezing (n = 125). Serum EDN levels were compared.Results: Serum EDN levels in the wheezing group were significantly higher than in the non-wheezing group (P < 0.001). The non-wheezing group was divided into three sub-groups: pneumonia, common cold, and tonsillitis. Serum EDN levels in the wheezing group were significantly higher than in the pneumonia, common cold, or tonsillitis subgroups (P < 0.001). There was no significant difference in serum EDN levels among the pneumonia, common cold, and tonsillitis subgroups.Conclusions: These findings suggest that elevated serum EDN levels could be a distinctive feature of respiratory infections with wheezing. EDN's utility as a biomarker for wheezing-associated disease should be explored through further study.