Air pollution continues to be a major public health concern affecting 9 out of 10 individuals living in urban areas worldwide. Respiratory tract is the organ most exposed to gas pollution, and ozone has been shown to be one of the most noxious pollutants to which living organisms are exposed. In the present work, we have investigated the effects of 0.1 ppm of ozone on chloride currents in human lung epithelial cells (A549 line) and whether this effect could be modulated by vitamin E pre‐treatment. Whole‐cell patch clamp technique was applied to not excitable cells in order to obtain information about chloride currents behavior, important for epithelial lung cells homeostasis. Significant alteration of the I–V curve after ozone treatment was observed, with the appearance of a large outward rectifier component decreasing over time and returning to the basal state levels after 24 h. Statistical analysis indicated a modification of the amount of ions passing the membrane in the unit of time as a possible cause of this difference. RT‐qPCR analysis showed an increase in ClC‐2 and ORCC mRNA after ozone exposure. In addition, pre‐treatment with vitamin E was able to suppress the outward rectifier component induced by ozone, bringing back the current values to the control level and preventing ozone induced chloride channels up regulation. Our data suggest that ozone exposure is able to modify chloride current density and the use of vitamin E can prevent the above‐mentioned damage. J. Cell. Physiol. 232: 1817–1825, 2017. © 2016 Wiley Periodicals, Inc. Pollutant ozone is able to induce oxidative stress to lung epithelial cells and this affect chloride currents and the expression of ClC2 and ORCC channel genes levels. Vitamin E pre‐treatment is able to rescue this noxious effect.