Background: Psoriasis is a common inflammatory disorder of the skin. Psoriasis is a disease of multifactorial origin where certain environmental factors acting on individuals with specific genetic predisposition leads to an immune dysregulation. Claudins are transmembrane proteins, which participate in the formation of tight junctions by binding to the actin cytoskeleton. Claudin‐3 present in the blood is considered as a useful biomarker of intestinal permeability. Objective: To evaluate serum level of claudin-3 in patients with psoriasis in comparison to control group and correlate its levels with disease severity. Patients and methods: Fifty-three patients (32 males and 21 females) with psoriasis and forty normal healthy control (23 males and 17 females) who matched the cases group as regard age and sex were included in this work. They were randomly selected from the Dermatology Department outpatient clinic in Mansoura University Hospital. Results: Psoriasis group showed significantly higher level of claudin-3 when compared to control group (mean=58.3 versus 41.2; p < 0.001). Smoking was significantly associated with higher Claudin-3 level (p=0.031). In addition, claudin-3 level increased gradually with increased severity grades (p < 0.001). No significant associations were found regarding claudin-3 level according to gender, nutritional status, family history, in psoriasis group (p>0.05 for each). Higher BMI, smoking and higher claudin-3 level were associated with prediction of higher PASI score in univariate analysis. While multivariate analysis revealed that only smoking and higher claudin-3 level were considered independent predictor of more severe psoriasis cases. Conclusion: Claudin-3 level was significantly higher in patients with psoriasis than healthy controls. PASI correlated with claudin-3 levels.