Bicarbonate is one of the major anions in mammalian tissues and fluids, is utilized by various exchangers to transport other ions and organic substrates across cell membranes and plays a critical role in cell and systemic pH homoeostasis. Chloride/bicarbonate (Cl /HCO ) exchangers are abundantly expressed in erythrocytes and epithelial cells and, as a consequence, are particularly exposed to oxidants in the systemic circulation and at the interface with the external environment. Here, we review the physiological functions and pathophysiological alterations of Cl /HCO exchangers belonging to the solute carriers SLC4 and SLC26 superfamilies in relation to oxidative stress. Particularly well studied is the impact of oxidative stress on the red blood cell SLC4A1/AE1 (Band 3 protein), of which the function seems to be directly affected by oxidative stress and possibly involves oxidation of the transporter itself or its interacting proteins, with detrimental consequences in oxidative stress-related diseases including inflammation, metabolic dysfunctions and ageing. The effect of oxidative stress on SLC26 members was less extensively explored. Indirect evidence suggests that SLC26 transporters can be target as well as determinants of oxidative stress, especially when their expression is abolished or dysregulated.