The study covers a thorough assessment of the overall degradation of diclofenac-Na (DCF) by high-frequency ultrasound, focusing particularly on identification, interpretation, and characterization of the oxidation byproducts and their reaction mechanisms. It was found that sonication of 5 mg L(-1) DCF at near neutral pH rendered complete conversion of the compound, 45 % carbon, 30 % chlorine, and 25 % nitrogen mineralization. Density functional theory (DFT) calculations confirmed the experimentally detected major byproduct 2,6-dichloroaniline, the formation of which was explained by OH• addition to the ipso-position of the amino group. The stability of UV absorption at around 276-280 nm throughout reaction was in agreement with the detected byproduct structures, i.e., the presence of amino/amine groups and phenolic, aniline, benzene, and quinine-type derivatives, which all absorbed at around the same band. Microtox toxicity of the reactor aliquots at early reaction showed that initially the reaction products, specifically 1-(2,6-dichlorophenyl)-2-indoline-one, were very toxic; subsequently toxicity exhibited a fluctuating pattern, and a steady declination towards the "non-toxic" level was observed only after 90 min. Oxygen uptake analysis also revealed the formation of harmful products at early reaction, but the reactor was totally biodegradable upon 1-h sonication.