Background: Obsessive-compulsive disorder (OCD), a chronically debilitating neuropsychiatric disorder, is characterized by distinctive and recurrent obsessions and/or compulsions. An increasing number of evidence indicates that sophisticated interactions between different neurobiological factors play a part in OCD etiology, but the certain underlying mechanisms are still mainly unknown. The present research aimed to explore whether the concentrations of serum zonulin and claudin-5 vary between OCD patients and healthy controls. The present research also intended to explore whether there is an association between zonulin and claudin-5 concentrations and OCD severity. Methods: Twenty-four (13 boys and 11 girls) OCD patients and 24 (13 boys and 11 girls) healthy controls were included in this study. The clinical severity of the OCD symptoms was evaluated by the Children's Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory. Participants also filled out the Revised Child Anxiety and Depression Scales-Child Version to determine the anxiety and depression levels of the children. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured. Results: Serum claudin-5 levels were found to be significantly higher in OCD patient whereas serum zonulin levels were not significantly different between the groups. Conclusions: Taken together with our results, our study suggests that dysregulation of the blood-brain barrier, especially claudin-5, may be involved in the etiology of OCD.