Reactive oxygen species (ROS) is both necessary and harmful in fundamental pathophysiological processes, depending on the concentration and location. In ROS-related research, reaction-based probes play a critical role in determining ROS concentration, ROS-sensitive drug delivery, and ROS-sensitive imaging. Along this line, the thioether moiety has been widely reported as a H2O2-sensitive trigger for drug delivery. The oxidation of a thioether by H2O2 to sulfoxide and/or sulfone has been proposed as the triggering mechanism. Through a number of straightforward kinetic experiments coupled with the literature findings, we show that such oxidation is expected to have long half-lives, likely on the scale of hundreds of hours at 10 µM of thioether concentration and 200 µM of H2O2. As such, thioether oxidation by H2O2 is unlikely to be a meaningful event under biologically relevant conditions for the purpose of ROS-sensitive drug delivery. On the other hand, we show that the second most abundant ROS, hypochlorite, can oxidize thioether at much faster rates with half-lives in the range of milliseconds at 10 µM each of thioether and NaOCl for a range of thioether with different substituents on the tethered aryl ring. Furthermore, oxidation of sulfoxide to sulfone is also feasible by NaOCl. Such information means that thioether-based drug delivery systems are likely to be activated by hypochlorite, but not H2O2.