Tetrathionates have been found in significantly high concentrations in recycled process waters from massive sulphide ore processing plants. These polythionates react with xanthate added to flotation pulps thus reducing xanthate dosages in solution potentially affecting flotation performance. The current study focused on the effect of the tetrathionate-xanthate reaction on sulphide mineral recoveries. Ore dissolution studies confirmed the generation of tetrathionates by copper-lead-zinc ores. In 20 min, the tetrathionates consumed more than half of the xanthate in solution at pH 7. Rest potential measurements and Fourier transform infrared spectroscopy (FTIR) showed that the degree of collector-mineral interactions of xanthate and both galena and chalcopyrite was greatly reduced in the presence of a 2000 mg/L tetrathionate solution. Microflotation tests showed that chalcopyrite recovery was less sensitive to tetrathionates as indicated by small changes in mineral recoveries. Galena was sensitive to the action of tetrathionates on the mineral surface as the galena recovery significantly declined when floated with xanthate as a collector in both a 500 mg/L tetrathionate solution and a 2000 mg/L tetrathionate solution. These fundamental results lay a sound base on which more discussion into the significance and the effect of tetrathionates on flotation performance of sulphide ores can be developed.