In this study, the effect of cations, Na+ and Mg2+, in saline water on copper flotation in the presence of calcium bentonite was investigated. It was found that as the concentration of NaCl was increased, the copper recovery initially decreased and then increased to above 99%, while the copper grade initially increased and then decreased. In contrast, as the concentration of MgCl2 was increased, the copper recovery continuously increased, while the copper grade continuously decreased. The variation of copper recovery and grade was mainly attributed to the synergistic effect of pulp rheology and flotation solution chemistry. The underpinning mechanisms are the compressing electrical double layer and ion-exchange interaction between saline water and bentonite, which occur at the same time. Using saline water slightly affected the pulp rheology with a decrease in copper recovery at low NaCl concentration. Increasing the concentration of cations in saline water might even facilitate the flowing out of exchangeable cations, especially divalent cations, from the interlayer space of bentonite to the solution, resulting in the decrease of copper grade at high salt concentration.