The present study combines surface analyses of pristine and leached low Fe-bearing and Pb-bearing sphalerite (PbS-ZnS) samples including XPS, GDOES, Raman spectroscopy, SEM and AFM, along with chemical evolution of leachates after 24 h of contact with 0.1 M NaOH, 0.1 M NaNO3, 0.1 M H2SO4 or 0.1 M HClO4 solution. A comprehensive electrochemical analysis using Cyclic voltammetry, Chronopotentiometry, Chronoamperometry, Linear sweep voltammetry and Tafel plots of PbS-ZnS and marmatite-like sphalerite (FeZnS) are conducted to compare its oxidation activities. Mineral characterizations reveal sluggish weathering linked to inhomogeneous and minor secondary polysulfides (Sn2−) surface compounds distribution, thus defining bare modifications of surface-activity relationships. The occurrence of secondary Zn-bearing compounds was not identified on altered samples, which suggests that this heavy metal diffuses into the bulk-solution. Electrochemical assessments confirm sluggish sphalerite oxidation mainly composed by two subsequent stages, where the highest mineral activity was obtained in NaOH conditions. It was found that the sphalerite oxidation is more active in the presence of Pb, while the activity of sphalerite gradually decreases when it is a mineral rich in Fe probably associated with progressive accumulation of Sn2−/S0 compounds. We suggest general oxidation mechanisms for sphalerite, and their environmental implications are discussed.