With justifiable concerns about reverse osmosis (RO) performance deterioration, as well as carcinogenic disinfection by-products, traditional oxidant, chlorine, has been replaced with disinfection process without those side effects. Chlorine dioxide, as an alternative disinfection agent, has been widely increasingly adopted in various water treatment facilities. To identify whether chlorine dioxide is applicable to the actual seawater RO desalination process, several lab-scale experiments were designed in simulating certain oxidant exposure circumstances.Activated properly with sulfuric acid, commercial chlorine dioxide solution was used for oxidizing feed solution. In the synthetic seawater, chlorine dioxide is shown to have better selectivity against chlorine, which has ‘chlorine demand’ as a disturbing factor. In comparison with baseline RO performance, the permeate flux of either spiking sodium hypochlorite solution as chlorine oxidant or chlorine dioxide solution showed different initial aspects; chlorine dioxide shifted permeate flux slope up instantly about 5% while maintaining its inclination compared with baseline, whereas chlorine spiking caused sudden steeper flux slope, which represented worse performance. Chlorine dioxide is shown not to chlorinate but to modify polyamide structure, as shown by the results of ATR-FTIR and SEM/EDX analyses and permeate flux inclination aspect under the reductant, sodium bisulfite.