Froth flotation of copper-zinc-lead ores is a complex task based on similar metallurgy processing and the strong connection between chalcopyrite and sphalerite. These types of ores represent 15% of the world’s production and 7.5% of copper deposits all over the world. In the present study, an attempt is made to assess the feasibility of froth flotation of a complex sulphide ore, where the effect of liberation grade, depressant, collector and frother dosages was studied. The main objective was to discuss the effect that the previous parameters cause on copper flotation performance. Copper flotation is dependent on the mineral liberation grade, which is significantly related with size distribution. Longer grinding times increased the Cu grade but decreased the recovery due to the presence of very fine particles. Lime and sodium metabisulfite achieved good flotation performance as depressants. The collector dosage is a sensitive parameter, although for this type of ore, lower dosages should be applied. Finally, a higher frother dosage led to a greater selectivity process, and reduced the entrainment of very fine particles, but also caused low kinetic ratios, and low valuable mineral recoveries. A well-defined flotation objective is imperative for a good liberation grade and reagents dosage selection, mainly for complex sulphide ores. A useful contribute has been given to a better technical understanding of the flotation process of complex sulphide ore from Moinho deposit.