The mining and mineral processing industries need water in all of their operations, from exploration, through mining and processing to closure. Flotation is the most affected by the quality of the process water in all of mineral beneficiation applications. Process water contains dissolved ions of almost all types depending on ore characteristics such as surface chemistry, mineralogy and surface oxidation. There is a general understanding about influence of individual ions on flotation performance in literature. However, it is crucial to demonstrate interactive effects of the major ions in a process water quantitatively using mathematical modelling to control the upper limits of ion contaminations. In this study the major ions affecting flotation performance of a complex Cu-Zn ore were determined to be Ca2+, Cu2+ and S2O32-. An experimental design has been done by using Design Expert Software. The statistical experimental design allowed derivation of mathematical models expressing grade and recovery as a function of water chemistry. These models were used to estimate critical concentration of the dissolved ions for an efficient flotation process.