The Sichuan-Yunnan-Guizhou metallogenic province of Southwest China contains more than 200 Mt of Pb-Zn ore in carbonate-hosted Pb-Zn deposits, representing ~ 27% of the total Pb and Zn resources of China. Sources of metals and pathways of ore-forming fluids were elucidated through a study of the Pb-Zn-S-Cd isotopic compositions of sphalerite from the Tianbaoshan, Fusheng, Maozu, Jinshachang, and Daliangzi carbonate-hosted Pb-Zn deposits. delta S-34 values indicate that S in the deposits is derived mainly from evaporites in Cambrian to Triassic sedimentary strata, sulfates coexisting with sulfides, and Meso-Neoproterozoic folded basement. delta Zn-66 values and Pb isotopic ratios indicate that these metals originate mainly from Sinian to lower Permian sedimentary rocks and Proterozoic basement. There is a trend towards isotopically heavier Cd and Zn compositions of sphalerite from Maozu to Daliangzi, Jinshachang, and Tianbaoshan, which are all hosted in the upper Sinian Dengying Formation. Previous studies showed that there would be a trend of enrichment in heavier Zn and Cd isotopes following the migration of fluids and precipitation of minerals. The above observations suggest that the ore-forming fluids of these deposits are probably derived from the same hydrothermal fluid system. The fluids most likely flowed through Maozu first, migrating along the Xiaojiang and Anninghe fault belts and their branch faults to Daliangzi, Jinshachang, and Tianbaoshan, respectively. Zn and Cd isotopes could be useful tools in tracing the pathways of ore-forming fluids in this district, and heavier Zn and Cd isotopic compositions could provide a geochemical fingerprint for detecting remote orebodies in large hydrothermal fluid systems.