Spectral interferences originating from instrumental and sample-matrix components continue to present a major analytical challenge to high-precision isotope ratio measurements by multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). This is particularly true when measuring stable isotopic variability of Cu and Zn, where instrumental and sample-matrix related spectral components may obscure the very small isotopic anomalies that typify these metals in terrestrial materials. We present a systematic characterisation and quantification of spectral interferences across the mass range 63Cu to 70Zn using two MC-ICP-MS instruments: a Micromass IsoProbe and a VG Axiom. Significant instrumental Ni backgrounds of up to 40 mV total Ni occur on the IsoProbe, reflecting streaming off the Ni-sampler and/or skimmer cones. This Ni contribution, however, is insufficient to account for the excess peak contribution at 64amu, suggestive of an as yet unidentified interference contribution at this mass. By contrast, Ni backgrounds on the Axiom are roughly one order of magnitude lower, and no comparable interference occurs at 64amu. High-resolution mass scans on the Axiom have identified 40Ar12C16O+ and 40Ar14N14N+ species at 68amu and 40Ar14N16O+ at 70amu. Also, HNO3-related 1H1H14N16O16O16O+ and 1H1H14N16O16O18O+ species at 64amu and 66amu respectively were observed on the Axiom using solution nebulisation. None of these species were observed on the IsoProbe, possibly reflecting the effect of an Ar-bled hexapole collision cell that reduces molecular interferences through ion-molecule reactions. Instrumental backgrounds have been successfully corrected using an on-peak acid blank subtraction procedure. Zinc hydride adducts occur on the Axiom using solution nebulisation. These interferences are eliminated using a desolvated plasma, and have been corrected by monitoring the 64Zn1H+/64Zn ratio on a pure Zn solution and applying an offline peak subtraction. No Zn hydride interferences were observed on the IsoProbe, suggesting differences in instrument design influence the formation and/or persistence of these species. Matrix-induced interference contributions on the Axiom and IsoProbe show increasing significance from argides (NaAr+, MgAr+, AlAr+) to oxide/hydroxide (TiO+, TiOH+, VO+, VOH+, CrO+, CrOH+) to double-charged species (Ba2+, Ce2+). Switching from solution nebulisation to a desolvated plasma enhances argide and double-charge species, and concurrently depresses oxides and hydroxides, reflecting changing conditions within the ICP-source. These results highlight the importance of removing problematic matrix components prior to Cu and Zn MC-ICP-MS isotope ratio measurements.