Despite the fact that when subjected to salinity stress most plants accumulate high concentrations of sodium (Na(+)) and chloride (Cl(-)) ions in their tissues, major research has however been focused on the toxic effects of Na(+). Consequently, Cl(-) toxicity mechanisms in annual plants, particularly in inducing oxidative stress, are poorly understood. Here, the extent to which Na(+) and/or Cl(-) ions contribute in inducing oxidative stress and regulating the adaptive antioxidant defense is shown in two Indica rice genotypes differing in their salt tolerance. Equimolar (100 mM) concentrations of Na(+), Cl(-), and NaCl (EC ≈ 10 dS m(-1)) generated free-radical (O2 (•-), (•)OH) and non-radical (H2O2) forms of reactive oxygen species (ROS) and triggered cell death in leaves of 21-day-old hydroponically grown rice seedlings as evident by spectrophotometric quantifications and histochemical visualizations. The magnitude of ROS-mediated oxidative damage was higher in sensitive cultivar, whereas NaCl proved to be most toxic among the treatments. Salt treatments significantly increased activities of antioxidant enzymes and their isozymes including superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, and glutathione reductase. Na(+) and Cl(-) ions showed additive effects under NaCl in activating the antioxidant enzyme machinery, and responses were more pronounced in tolerant cultivar. The expression levels of SodCc2, CatA, and OsPRX1 genes were largely consistent with the activities of their corresponding enzymes. Salt treatments caused an imbalance in non-enzymatic antioxidants ascorbic acid, α-tocopherol, and polyphenols, with greater impacts under NaCl than Na(+) and Cl(-) separately. Results revealed that though Cl(-) was relatively less toxic than its counter-cation, its effects cannot be totally ignored. Both the cultivars responded in the same manner, but the tolerant cultivar maintained lower Na(+)/K(+) and ROS levels coupled with better antioxidant defense under all three salt treatments.