The aim of the study was to determine oxidation potential of selected persistent, environmentally relevant antibiotics (Amoxicillin, Levofloxacin, and their mixture with Vancomycin) to reduce their environmental emissions. Ozonation (O3) and indirect ozonation at pH 9.5 (O3/pH9.5) were catalytically enhanced by addition of Fe2+ (O3/Fe2+) and photocatalytic ozonation in combination with Fe2+ and UV-A black light (O3/Fe2+/UV) at two temperatures using total organic carbon (TOC) and chemical oxygen demand (COD) to identify formation of by-products. Oxidative degradation followed pseudo-first order consecutive reactions. Initial phase of oxidation was more intensive than mineralisation at 21 and 40 °C: up to 57.3% and 69.2%, respectively. After 120 min mineralization at 21 °C was up to 64.9% while at 40 °C it was up to 84.6%. Oxidation reached up to 86.6% and 93.4% at 21 °C and 40 °C, respectively. The most efficient processes were indirect ozonation at pH 9.5 (O3/pH9.5) (up to 93.4%) and photocatalytic enhanced ozonation with Fe2+ and UV-A black light (O3/Fe2+/UV) (up to 89.8%). The lowest efficiency was determined in experiments with direct ozonation (up to 75.5%). Amoxicillin was the only one completely mineralised. Study confirmed that ozonation with addition of Fe2+ and UV radiation has the potential to improve efficiency of the antibiotic-removal processes. Further experiments varying amounts of Fe2+ and other experimental conditions should be accomplished to set up more general methodological approach for reduction of antibiotics emissions.