Background: Vitiligo is a chronic acquired skin disorder that causes loss of its colour. The definite cause is unknown but may be due to genetic factors, immune system changes or stress exposure. Oxidative stress may cause melanocytic destruction through its damaging effects on the cell components. Objective: Measurement of E-cadherin and hydrogen peroxide (H₂O₂) level in vitiligo patients versus controls. Patients and Methods: Thiscase-control study involved 20 sex and age matched participants, 10 active non segmental vitiligo (NSV) patients, and 10 non vitiliginous controls, all recruited from the Dermatology Department, Ain Shams University and New Cairo Police Academy Hospital from March 2018 till March 2021. Skin biopsies were taken from four different anatomical sites in cases and controls for immune-histochemical evaluation of E-cadherin and biochemical measurement of H₂O₂. Results: H₂O₂ showed statistically significant higher values, while E-cadherin had significantly lower staining in patients than controls. Conclusion: Higher H₂O₂ level, in vitiligo patients, is suggestive of oxidative stress. Current study may indicate that vitiligo is not just a disease of melanocytes, but keratinocytes may also play a role, as well. Keratinocytes in depigmented epidermis may have a changed microenvironment, as evidenced by a lack of cell-to-cell adhesion between keratinocytes and melanocytes, as well as between keratinocytes, disrupting the skin pigmentary system.