As part of the process optimization project of CMG (Mining Company of Guemassa-Marrakech, Morocco), a preliminary study on the effect of water quality on the flotation of galena, sphalerite, chalcopyrite, and pyrrhotite was carried out using asymmetrical fractional factorial design. The multivariable analysis showed that of ten studied factors, six (Cu2+, Zn2+, Mg2+, Ca2+, SO42-, and PAX) have a significant influence on the flotation of these sulphide minerals. Graphical analysis showed that high concentrations of Cu2+ (7-14 mg/L) in synthetic process water increased the recovery of galena, chalcopyrite, sphalerite, and pyrrhotite. At low Cu2+ concentrations (0-7 mg/L), sphalerite was depressed. Zn2+ at low concentrations (0-20 mg/L) decreased the recovery of all studied minerals. However, at high concentrations (20-40 mg/L), an increase in chalcopyrite, sphalerite, and pyrrhotite recoveries was observed. Mg2+ (100-200 mg/L) decreased the recovery of galena, chalcopyrite, and sphalerite. Ca2+ (1200-2000 mg /L) depressed sphalerite flotation. Sulphate ions (SO42-) enhanced recovery of all the studied minerals. Potassium amyl xanthate (PAX) promoted sphalerite recovery at high concentrations (10-20 mg/L).