Magmatic activity plays an important role in mineralization, but little is understood of its role with respect to carbonate-hosted stratabound epigenetic Pb\\Zn deposits. The Fule Pb\\Zn deposit (~10 Mt of sulfide ore with mean grades of 15–20 wt% Zn + Pb), is stratigraphically placed in middle Permian strata and spatially (~1 m) associated with late Permian continental flood basalts of the Emeishan Large Igneous Province (ELIP). It thus provides an ideal case to investigate its genetic relationship with the ELIP. In addition, the Fule deposit is characterized by high concentrations of Ag, Cd, Ge and Ga, and contains a variety of Cu and Ni sulfide minerals. Syn-ore calcite (δ13C = +2.57–+3.01‰) and associated fluids (δ13C = +2.96–+3.40‰) have δ13C values similar to those of fresh limestone (δ13C = +1.58–+2.63‰), but the δ18O values of calcite (+16.83–+19.92‰) and associated fluids (+7.80–+10.89‰) are distinctly lower than those of limestone (δ18O = +21.85–+23.61‰). This means that C is mainly derived from limestone, whereas the O isotope signature may be related to water/ rock (W/R) interaction between mantle and/or metamorphic fluids and limestone. δ34S values of sulfide minerals obtained by in situ NanoSIMS and conventional bulk techniques record a range of +9.8–+23.1‰ and +10.04–+16.43‰, respectively, reflecting the enrichment of heavy S isotopes in the ore-forming fluids and thermochemical sulfate reduction (TSR) is the principal mechanism for the formation of S2−. Cores of sulfide crystals have much higher δ34S values than their rims, indicating a probable mixture of multiple S reservoirs and/or a dynamic fractionation of S isotopes occurred during sulfide precipitation. The uniform femtosecond (fs) LA-MCICPMS in situ Pb isotopic data for galena plot in the field that differs from any of the three potential sources in the region. Such signatures demonstrate that metal Pb was most likely derived from a well-mixed source of basalts, sedimentary rocks and basement rocks. We propose that (a) the enrichment in Ag, Cu, Ni, Cd, Ge and Ga, and the isotope signatures of hydrothermal minerals in the Fule region are related to fluids derived from or flowed through multiple reservoirs; (b) Emeishan magmatism provided heat, elements and associated fluids, and its basalts acted as an impermeable and protective layer; and (c) fluid mixing caused TSR, and then resulted inW/R interaction and CO2 degassing, all of which played a key role in the precipitation of hydrothermal minerals.