It has been well established that metal and sulfur sources in mineral deposits can be very difficult to identify, especially for ore deposits hosted in sedimentary rocks. Using the world's largest Sb deposit at Xikuangshan in southern China as a case study, this study combined Hg isotopes and in situ sulfur isotope measurements to constrain the sources of Sb and sulfur. A variation of 1.1 parts per thousand in delta Hg-202 (0.04 to 1.15 parts per thousand) was observed in stibnite ore samples, suggesting that mass-dependent fractionation of Hg isotopes occurred during the formation of the deposit. Significant mass-independent fractionation of Hg isotopes, with o(199)Hg ranging from - 0.03 to - 0.17 parts per thousand, was also observed in the ore samples, suggesting that Hg transported by the ore fluids was inherited from Proterozoic basement metamorphic rocks as these rocks show similar o(199)Hg signatures (- 0.03 to 0.07 parts per thousand). In situ sulfur isotope measurements yielded delta S-34 values that cluster in the range of + 6.8 to + 10.2 parts per thousand, providing evidence that sulfur contained in ore fluids may also have been dominantly derived from underlying Proterozoic basement metamorphic rocks (delta S-34 = +5.6 to + 11.5 parts per thousand). Using the new results from Hg and S isotopes, we proposed that deep-circulated meteoric water mobilized Sb, Hg, and S from the Proterozoic metamorphic basement, ascended along deep faults, and subsequently deposited Sb at favorable structural zones as a result of boiling of the hydrothermal fluids, generating the world-class Xikuangshan Sb deposit. This study also highlights the combined use of Hg-S isotopes as a novel method to provide new and additional insights into the source regions of ore materials for sedimentary-hosted Sb deposits.