Mineral processing utilizes large amounts of water and aims to reduce water consumption by recirculation and closing the water loops. This results in accumulation of chemical and biological contaminants in process water that may have adverse outcomes on the process performance. To optimize water quality suitable for each process step and plant, knowledge of both chemical and biological effects are needed as well as techniques to best remove the contaminants. This study focused on the consequences of microorganisms, enriched from the actual process earlier, on the flotation performance in the multi-metal Kevitsa mine in Northern Finland and the applicability of ion exchange for the removal of dissolved sulfur species and microorganisms from water. The increase of microbial load from the original 106 to added 107 16S rRNA copies mL−1 affected positively the flotation selectivity, especially in the case of nickel. Two tested water types, process water (PW) and final tailings water (FT), behaved slightly differently. In the Cu flotation phase added microorganisms did not affect the Cu recovery of FT but decreased significantly the recovery of Cu in PW. With equal Cu grade, the recovery was as high as approximately 25 percentage points lower. However, added microorganisms in both water types decreased notably the recovery of Ni in Cu concentrate (18 to 37 %-points). At the same time the amount of Ni recovered in the Ni concentrate increased by 18 to 33 %-points with added microorganisms. Visually the froth layer was higher and more stable in the Ni flotation in experiments with added microorganisms compared to experiments without added microorganisms. The concentrations of dissolved sulfate and thiosulfate ions were low in the studied waters compared to operations treating massive sulfide ores and did not significantly affect the flotation performance. For this reason, the IX water treatment was not required for these ions. However, the IX treatment proved to be effective in removing both sulfur species and microorganisms. The use of dissolved air flotation (DAF) was a successful pretreatment for ion exchange in removal of microorganisms. However, microorganisms are not usually taken into consideration when process performance or water cleaning techniques are designed and optimization could result generally in even better outcome.