This study reports the heterogeneous activation of sodium persulfate (SPS) by La0.8Sr0.2CoO3-delta (LSC) perovskite oxide for the degradation of sulfamethoxazole (SMX), a representative antibiotic agent. LSC was synthesized by a combustion method and characterized with respect to its physicochemical characteristics by means of nitrogen isotherm absorption (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM/EDS) and transmission electron microscopy (TEM/HRTEM). LSC showed high activity towards SPS activation, resulting in complete SMX degradation in short time periods. The effect of SPS (100-500 mg/L), catalyst (100-500 mg/L) and SMX (0.125-0.5 mg/L) concentrations, as well as initial solution pH on SMX removal was studied. Apart from ultrapure water (UPW), additional experiments were conducted in bottled water (BW) and secondary treated wastewater (WW), showing the existence of retarding phenomena in SMX degradation. In order to further investigate these phenomena, experiments in UPW spiked with bicarbonate or chloride ions and humic acid were also carried out. The role of reactive oxygen species (sulfate and hydroxyl radicals) was determined with the use of suitable scavengers (methanol, t-butanol). Catalyst stability was assessed for five consecutive runs showing LSC superior recyclability. Coupling activators (LSC with simulated solar irradiation) resulted in faster SMX degradation in a synergistic rather than cumulative way.