The generation of Reactive Oxygen Species (ROS), H2O2 and OH, has been observed from sulfide mineral containing particles in acidic solutions. The implications of this phenomenon, as a potential microbial stress-causing effect, have been studied previously with respect to thermophilic bioleaching performance in the presence of finely milled pyrite and chalcopyrite concentrates. In this study, the effect of sulfide mineralogy on ROS generation in the absence of microbes under physicochemical conditions typical for the bioleach environment was investigated. The mineralogical and elemental composition of eleven different samples containing sulfide mineral was obtained. These Au, Cu and other base metal-containing sulfide mineral concentrates as well as a milled whole ore of low Cu grade were tested for ROS generation. The whole ore sample and two refractory Au concentrates containing approximately 50% pyrite, generated significantly less ROS compared to the base metal-containing concentrates when compared on a constant surface area loading basis. Sulfide mineral-related variables were correlated with ROS generation. A significant difference was observed between FeS2 and CuFeS2 grades separately, whereas a combined measure of both minerals present in samples showed a consistently strong correlation to ROS generation. The Cu grade, total Cu-containing sulfides and the chalcopyrite content of Cu-containing samples correlated well with ROS generation. However, a common deterministic variable with a strong association to increased ROS generation was not found. A sub-set of samples were subjected to QEMSCAN® for textural analysis. Results suggested that a decrease in sulfide mineral liberation, caused by gangue silicate mineral occlusion to solution, resulted in decreased reactivity as shown in one of the Au-containing samples. Well-liberated chalcopyrite and pyrite phases corresponded to increased reactivity of samples. Pyrite, which was present in all of the reactive samples, was shown to be associated with other sulfide minerals, implicating its importance in galvanic interactions. Micro-analysis of chalcopyrite and pyrite phases from highly reactive samples showed an abundance of particles with extensive cracking and the possible presence of secondary transformation phases (szomolnokite). These results suggest that sulfide mineralogy, liberation and extent of physical processing affect sulfide mineral concentrate reactivity in acidic solutions.