Background: An inflammatory chronic illness is psoriasis. The body of research on the gut microbiota and its function in homeostasis has expanded recently. Psoriasis pathogenesis is significantly influenced by changes in the gut microbiota. Objective: Our study aimed to determine the link between non-invasive measures of intestinal barrier integrity in psoriasis patients and disease severity. Patients and methods: This is a case-control study that was conducted to investigate the relationship between claudin-3 and I-FABP levels and psoriasis vulgaris.The subjects were divided into two groups:Group A (patients group) included 50 patients with chronic plaque psoriasis, and group B (control group) included 40 non-psoriatic healthy volunteers who matched the patient group as regard age, sex and BMI. They were chosen because they did not have any autoimmune, inflammatory, or systemic infections, and they were not taking any medication. Results: Serum claudin-3 level was higher in patients with psoriasis compared to healthy control (mean, 41.84 ± 9.13 vs 33.77 ± 7.45 ng/mL, P < 0.001) and the mean claudin-3 of mild, moderate and severe patients subgroups were 36.08 ± 7.87, 42.30 ± 5.66 and 50.20 ± 5.52 ng/mL respectively (P <0.001). Patients with psoriasis also had elevated level of serum I-FABP (307.2 ± 143.1 vs 222.5 ± 40.14 pg/mL, P 0.004) and I-FABP was statistically higher in severe subgroup (419.81 ± 147.23) and moderate subgroup (340.05 ± 164.28) as compared to mild subgroup (218.43 ± 37.80) (P < 0.001). Conclusion: Claudin-3 and I-FABP (non-invasive indicators of intestinal integrity) were elevated in psoriasis and correlated with disease severity. More research is needed to evaluate whether strengthening the intestinal barrier can be a novel treatment target in psoriasis.