Previous studies have shown that the floatability of chalcopyrite in seawater at highly alkaline conditions is significantly affected by the presence of clays. The reason is that the species of calcium and magnesium present in seawater under those conditions may act as a bridge between the surfaces of clay and chalcopyrite, generating massive aggregates that then depress. In this context, the objective of this work is to analyze the impact of pretreated seawater with low amount of calcium and magnesium ions on the recovery of a sulphide copper mineral with high kaolinite content as clay. The seawater pre-treatment is done by the addition of sodium hydroxide in a high carbon dioxide environment. The chemical reactions realized under these conditions lead to the formation and precipitation of calcium and magnesium species that are subsequently removed by vacuum filtration. The pre-treated seawater is then used in flotation tests at pH 11 for copper sulphide, where the mineral is synthetically prepared by mixtures of chalcopyrite, kaolinite, and quartz. When comparing the flotation results for different types of water, including seawater and pre-treated seawater, a significant effect is observed: as the seawater hardness decreases, which comprises the calcium and magnesium ions, the recovery of chalcopyrite is increased. However, the effect is markedly enhanced in the presence of kaolinite. Therefore, the results indicate that sodium hydroxide and carbon dioxide are able to remove different species of calcium and magnesium from seawater and could improve the chalcopyrite recovery with high kaolinite content.