The mining industry often must mix different kinds of water on the mine site during pre-treatment or post-treatment before the final discharge of the treated water to the environment. Microbubble ozonation has proven to be efficient in the removal of contaminants of concern from mine water, such as metals, metalloids, and nitrogen compounds, which can persist in the environment and entail toxicity issues. This study evaluated the efficiency of ozone microbubbles combined with lime precipitation on contaminant removal and its impact on toxicity for Daphnia magna with five different mine effluent mixes from an active mine site located in Abitibi-Témiscamingue, QC, Canada. For the non-acidic mixes, two scenarios were tested: first, pre-treatment of metals using lime precipitation and a flocculant was conducted prior to ozonation; and second, ozonation was conducted prior to metals post-treatment using the same precipitation and flocculation technique. Results showed that the NH3–N removal efficiency ranged from 90% for the lower initial concentrations (1.1 mg/L) to more than 99% for the higher initial concentrations (58.4 mg/L). Moreover, ozonation without metals pre-treatment improved NH3–N treatment efficiency in terms of kinetics but entailed abnormal toxicity issues. Results of bioassays conducted on water with metals pre-treatment did not show any toxicity events but showed abnormal toxicity patterns on the mixes treated without metals pre-treatment (diluted effluents were toxic, while undiluted were not). At 50% dilution, the water was toxic, probably due to the potential presence of metal oxide nanoparticles. The confirmation of the source of toxicity requires further investigation.