This study demonstrates the effects of a potassium propyl xanthate (PPX) collector and sodium sulfite (Na2SO3) depressant on pure chalcopyrite in synthetic seawater (SSW) and potassium chloride (KCl) solutions. SSW solutions with 35 g/L of salt and 0.01-M KCl were used for microflotation and zeta potential tests. Particles sized between 200# and 100# (75–150 µm) were used, and the pH was between 8.0 and 8.5. The surface of the mineral and its interaction with the collector were characterized using Raman spectrometry. The zeta potential of the chalcopyrite was measured in KCl solution at a pH range of 3–12 using the collector and depressant at a monodispersed particle size of 635# (20 µm). The results indicate that the floatability of chalcopyrite is not affected by the presence of PPX collectors in SSW solutions. SSW provides better recoveries than KCl solutions with values of 91.42% and 88.15%, respectively. The Na2SO3 depressant does not hinder the mineral floatability throughout the entire concentration range used; however, special care must be taken when adjusting the pH range to avoid increasing the zeta potential.