Organic compounds contained in urine, such as urea and creatinine, can compete with pharmaceuticals for the electro‐generated oxidants during electrochemical treatment. In addition, urine has a large amount of chloride ions, creating opportunities to produce chlorine and aqueous‐free chlorine species via electrolysis. The aim of the present study is to analyze artificial urine as a supporting electrolyte, while studying the removal of the organic components present (urea and creatinine) by employing an experimental design approach. A 2³ factorial design was employed to evaluate the efficiency of the photo‐assisted sonoelectrochemical (EC/UV/US) process. Operating conditions were optimized using response surface methodology (MRS), namely: 11.44 mL min−1 flow, 1.940 A at 160 min. The pH was analyzed and a predominance of HOCl (pH < 7.0) can be observed. Response surface methodology was used to investigate the effects and interactions of flow rate, time, and current to track the removal efficiency of organic compounds contained in artificial urine (TOC, creatinine, and urea). Over prolonged electrolysis, the EC/US/UV process achieved removal of TOC (25.7%), creatinine (68.2%), and urea (33.3%), due to the large contribution of highly reactive radical species (•OH, •Cl, ClO−).