This study investigates Cu isotope ratio variations in the high-grade, vein-type Cu-Ag deposit of Dikulushi, Democratic Republic of Congo. The Dikulushi deposit consists of a Cu-Pb-Zn-Fe mineralization, comprising sphalerite, chalcopyrite, bornite, and chalcocite that precipitated under reducing conditions. This mineralization was partly remobilized in more oxidizing conditions into a Cu-Ag mineralization phase, which is dominated by Ag-rich chalcocite. The upper part of the deposit is strongly reworked by weathering. Sulfides from the two types of mineralization and Cu carbonates/-silicates from the weathering zone display significant Cu isotope ratio variations. Chalcopyrite and chalcocite from the Cu-Pb-Zn-Fe and Cu-Ag mineralization types are characterized by variable low Cu isotope compositions (0.00 to −2.3‰ δ65Cu). The Cu isotope composition for some chalcocite from the Cu-Ag mineralization deviates to lower δ65Cu values relative to that of chalcocite from the Cu-Pb-Zn-Fe mineralization. This deviation is likely related to remobilization of the Cu-Pb-Zn-Fe mineralization in an oxidizing environment. The isotopic composition of Cu in chalcocite from both mineralization types becomes higher toward the center of the orebody and as a function of depth. This variation could be related to physicochemical changes in the precipitation environment as a consequence of interaction of the reduced mineralizing brine with the oxidized host rock or might have been induced by supergene processes afterward. The supergene mineralization is composed of malachite, azurite, and chrysocolla that are enriched in 65Cu (1.37–2.65‰ δ65Cu).