Epithermal Au-Ag deposits of the La Carolina district, in the San Luis metallogenetic belt (Argentina), are related spatially and genetically to Mio-Pliocene volcanism. In this district, mineralization in the Cerro Mogote and Puesto La Estancia prospects occur as disseminations, veins and fracture/cavity infillings in volcanic/pyroclastic rocks, metamorphic basement and hydrothermal breccias. The gangue assemblage is dominated by carbonates (siderite, rhodochrosite, kutnahorite, dolomite). The main sulfides are pyrite, sphalerite, galena and chalcopyrite. Pyrite and sphalerite have compositional zoning, the former with As-rich cores and Cu-rich overgrowths, the latter with Fe-rich and Fe-poor bands. Sphalerite shows variable contents of Mn, Cu, In, Ga, Ge and Ag. The In-richest sphalerite hosts up to 5940 ppm In but also contains elevated concentrations of Cu, Ag, Ga and Ge, suggesting a coupled substitution mechanism resulting in enrichments in monovalent (Ag+, Cu+) and trivalent-tetravalent cations (Ga3+, In3+, Ge4+). The main precious metal minerals are Ag-rich tetrahedrite, acanthite, argyrodite, pearceite–polybasite and Au-Ag alloy. Locally, Se and/or Te-enriched minerals include galena Pb(S0.9–1Se0.1–0), hessite Ag2(Te0.9–1Se0.1–0), Se-rich cervelleite Ag4(Te1.3–0.9S1–0.5 Se0.5–0.2), and also alburnite [Ag8GeTe2S4] and benleonardite [Ag15Cu(As,Sb)2S7Te4]. Pearceite contains Te (3.6–4.3 wt.%) and Se (1–2.3 wt.%) substituting for S, which are unusually high concentrations for this mineral. The Puesto La Estancia deposit contains various tellurides including sylvanite, petzite, stutzite, altaite, tellurobismuthite and volynskite. This study shows that the chemistry of the fluids fluctuated during ore deposition suggesting different fluid pulses (system rejuvenation and/or boiling). The enrichment in Te, Se and Bi enrichment is supportive of a magmatic contribution to the ore fluid, while graphite in the metamorphic basement could be the source of germanium, although a magmatic source cannot be ruled out.