In the present study, the efficiency of immobilized CuOx catalyst for sodium persulfate (SPS) activation was investigated. The efficiency of the CuOx/SPS system was evaluated for sulfamethoxazole (SMX), an antibiotic agent, degradation. CuOx nanoparticles were grown on TiO2 pellets, serving as supporting material. Information about the morphology and physicochemical characteristics of the catalyst was obtained by means of BET, SEM and XRD. The activity of CuOx/SPS system was first studied in a batch reactor resulting in complete 0.5 mg/L SMX removal in 90 min. SMX degradation followed pseudo-first-order kinetics. The effect of SPS (100-500 mg/L) concentration was also tested. Additional experiments were carried out under simulated solar irradiation showing the existence of synergistic phenomena. The performance of the CuOx/SPS system was further evaluated under real and synthetic water matrices. Apparent rate constant decreased from 0.028 min(-1) in ultrapure water to 0.007 min(-1) and 0.003 min(-1) in the case of bottled water and wastewater, correspondingly. SMX removal was mainly hindered by the presence of bicarbonate. The by-products of SMX degradation were identified by LC-MS-TOF. In order to investigate the long-term performance of the present system, the CuOx/SPS process was operated in a continuous-flow mode at a flow rate of 0.56 mL/min (corresponding to residence time of 40 min); under these conditions, SMX removal remained remarkably stable at similar to 80 % for 118 h or operation.