Fe isotope compositions of bulk samples from Gaosong ore deposit in Gejiu district, SW China were investigated and an overall variation in δ56Fe values from −0.33‰ to +0.20‰ has been observed. In this study, the δ56Fe values of primary sulfide ores are lower than the oxidized ores, while the iron isotope compositions of gossan samples, which represent highest oxidation degree, are heavier than the oxidized ore samples. These data indicate that iron isotopes experienced fractionation during supergene weathering process, furthermore, heavier iron isotopes enriched in more oxidized products. Another highlight is the Fe isotope compositions that are affected by mineralogy, which is considered as the primary mechanism of the large Fe isotopic variations in the primary ores. Enrichment of light iron isotopes in primary sulfide ores suggests that iron isotopes fractionated during fluid exsolution from its parental magma and the Fe source of skarn ores is mainly the magmatic source. This observation that significant Fe isotope fractionation occurs in supergene weathering process and fluid exsolution process provides an example in using Fe isotopes to trace supergene geochemical cycling and ore deposit formation/evolution processes.