The aim of this research was to assess whether or not changes in the concentrations of serum zonulin and claudin-5 in patients with schizophrenia could have etiopathogenetic importance. In previous studies, the data regarding the relationship between intestinal and blood-brain barrier (BBB) permeability and the etiology of schizophrenia have been limited. In this study, we assumed that there may be a difference in serum zonulin and claudin-5 levels in patients with schizophrenia, which may affect the severity of the disease. Fifty schizophrenia patients and 50 healthy controls were included in this study. The patients were administered the Positive Symptoms Assessment Scale (SAPS) and Negative Symptoms Assessment Scale (SANS) to determine the severity of symptoms. Venous blood samples were collected, and the serum zonulin and claudin-5 levels were measured. The mean serum zonulin levels were significantly increased in patients with schizophrenia when compared to the control group. Serum claudin-5 levels were decreased in the schizophrenia patients when compared to the controls. The present study indicates that zonulin is increased and claudin-5 is decreased in patients with schizophrenia. These findings extend the existing knowledge on the dysregulation of intestinal permeability, especially zonulin, and BBB, especially claudin-5, and show that both proteins may be involved in the etiopathogenesis of schizophrenia.