In the flotation of copper ores, several processing plants report that copper recovery is affected by the proportion and reactivity of pyrite in the ore, with the effect becoming more intense when the feed particles are finer as a result of regrinding. In this work, a mixed model mineral system consisting of chalcopyrite (CuFeS₂) and pyrite (FeS₂) with varying pyrite content (20–80 wt.%) was used to investigate the effect of pyrite on the pulp chemistry and chalcopyrite recovery. Flotation tests showed that chalcopyrite flotation rate, recovery and grade, as well as the pulp oxidation potential, decreased with increasing pyrite content whilst pyrite recovery increased. Surface analysis (XPS, ToF-SIMS and EDTA) indicated that copper activation of pyrite increased with increasing pyrite content, facilitating pyrite recovery. The decrease in chalcopyrite recovery can be attributed to increased surface oxidation.