Objectives: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by obsessions and compulsions, with a prevalence of 1%–3%. Tight junction (TJ) proteins contribute to maintaining the epithelial barrier. This study investigated the association of serum TJ-associated MARVEL protein family and inflammatory markers with OCD severity in children and adolescents. Methods: A total of 43 drug-naive children with “pure” OCD and 37 age-matched healthy controls were included in the study. Serum levels of occludin, tricellulin, MarvelD3, which belong to the TJ-associated MARVEL protein family, along with inflammatory markers (C-reactive protein, tumor necrosis factor-alpha [TNF-α], interleukin-6) were assessed. The severity of OCD was ascertained using the Maudsley Obsessive-Compulsive Inventory (MOCI). Biochemical data of patients and control groups were compared against clinical features such as OCD severity and time since symptom onset. Results: Both groups showed similar sociodemographic factors, except that psychiatric disorders and family histories of OCD were significantly higher in the OCD group. Although serum TJ levels were not significantly different between groups, serum tricellulin (r= 0.427, p=0.004), MarvelD3 (r=0.489, p<0.001), and TNF-α (r=0.495, p<0.001) levels had a positive correlation with the severity of OCD based on MOCI. Conclusion The findings suggest that tricellulin, MarvelD3, and TNF-α may be associated with OCD severity. Further comprehensive research is required to determine the role of TJ proteins belonging to the MARVEL protein family in the pathophysiology of OCD.