Metallurgical applications of deep eutectic solvents (DESs), known as ionometallurgy, have received significant research attention in recent years. While many studies claim that DESs are generally green and enhance process efficiency, others believe that industrial applications of ionometallurgy are generally not viable. Here, we report on leaching experiments of a sulfide flotation concentrate using ethaline, a chloride-based DES, in the presence of common oxidants. Following a mineral-based approach, we compare results with those obtained from aqueous chloride solutions to assess the influence of the leaching medium. We aim to contribute to a basic understanding of key differences between DESs and aqueous solutions and hope that this will help to make informed decisions about the suitability of DESs for leaching applications. Experiments were performed on a feed concentrate comprising a mixture of sulfide minerals along with substantial concentrations of Au, Ag, and Te. We found similar leaching behaviors for ethaline and aqueous solutions in nonoxidative leaching. However, when oxidizing agents were introduced, ethaline exhibited higher leaching efficiencies. Notably, the oxidation rate of pyrite in ethaline was very low, while chalcopyrite exhibited high oxidation rates. Furthermore, the results highlight significant variations in leaching rates depending on the type of oxidant, with the highest rate observed for I 2 , followed by CuCl 2 , and FeCl 3 . H 2 O 2 and O 2 were less effective. The leaching of gold−silver tellurides was possible in ethaline. This could be of particular significance, given that Au−Ag−Te compounds pose challenges in conventional cyanide treatment.