Pyrite has natural floatability and thus readily enters valuable mineral flotation concentrates, diluting their quality and decreasing their economic value. Its separation is challenging, depending on process conditions, the presence of activating ions, and water quality, particularly in regions where seawater is used. This study examines the effect of various doses of sodium metabisulfite (SMBS) on pyrite depression in freshwater and seawater under weakly alkaline conditions and with different copper ion concentrations. Without the addition of activators or depressants, pyrite recovery is 40% in freshwater and 60% in seawater, whereas with 10 ppm of SMBS, recoveries drop to 28% and 38%, respectively. The addition of 10 ppm Cu²⁺ increases recovery by 10% in freshwater and by 20% in seawater. In the presence of 75 ppm of PAX, maximum recovery reached 50% in freshwater and 80% in seawater. These results suggest that cationic bridges formed by seawater ions, combined with CaOH⁺ activation, play a critical role in pyrite activation, even in the presence of depressants.