Sodium chlorite (NaClO ) is used in the production of chlorine dioxide for bleaching and stripping of textiles, pulp, and paper. It is also used as disinfectant in municipal water treatment and as a component in therapeutic rinses and gels. The effect of NaClO on human erythrocytes has been studied under in vitro conditions. Incubation of 5% suspension of erythrocytes with NaClO (0.1-2.0 mM) at 37°C for 30 min resulted in marked cell lysis (1.2-3.8 fold) and increased their osmotic fragility. Several parameters were assayed in cell lysates prepared from NaClO -treated and -untreated (control) erythrocytes. Compared to controls, exposure to NaClO caused significant increase in protein oxidation (1.1-8.07 fold), lipid peroxidation (1.08-4.95 fold) with decrease in total sulfhydryl (-5 to -61%), and glutathione levels (-7 to -86%). Methemoglobin content was tremendously increased, by 5-52 fold when compared to control, while methemoglobin reductase activity decreased (-17 to -93%) upon NaClO treatment. NaClO enhanced the generation of reactive oxygen species by 3-21 fold and lowered the metal reducing and free radical quenching ability of erythrocytes. It also caused an increase in nitric oxide levels (2.7-15.4 fold) showing generation of nitrosative stress too. The activities of major antioxidant and membrane bound enzymes were significantly altered. Gross morphological changes, from discocytes to echinocytes, were seen in NaClO -treated erythrocytes under electron microscope. These results show that NaClO induces oxidative stress in human erythrocytes, damages the membrane, and impairs the cellular antioxidant defence system. This oxidative damage can shorten the life span of erythrocytes in blood resulting in red cell senescence. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1343-1353, 2017.