The sulfamethoxazole (SMX) mineralization through the solar photo electro-Fenton (SPEF) process in a pilot plant containing 20 L of 50 mg L-1 SMX solution was investigated. The process was carried out at pH 3 under different operational conditions varying temperature, volumetric flow and applied current density. Box-Behnken experimental design and response surface methodology (RSM) were used to optimize the experimental variables of the SPEF process. Under the optimal conditions, the SPEF was compared with electro-Fenton (EF) and anodic oxidation (AO-H2O2) processes. Under optimum design variables of 47 mA cm(-2), 45 degrees C and 571 L h(-1), SPEF was more efficient yielding 90% of TOC removal after 360 min of reaction with a maximum of 83% of mineralization current efficiency (MCE). The main by-products detected on the final solution treated by SPEF were oxalic, maleic, oxamic and fumaric acids, while NH4 (+) and NO3- were the main inorganic nitrogen ions released during the process.