Literature describes a kinetic degradation profile for sulfamethoxazole (SMX) and trimethoprim (TMP) antibiotics in aqueous solutions using a photo-Fenton reaction characterized by a very fast initial reaction rate followed by a slow degradation process. This work tries to elucidate that the slow decay on SMX and TMP concentration observed in the second part of the photo-Fenton kinetic degradation profile is not only entirely attributed to the competition of hydroxyl radicals between the initial intermediates generated and the antibiotic molecules, but also associated to the formation of strong and stable Fe(III)-antibiotic complexes, which limits the photoreduction of Fe3+, decreasing the decomposition of H2O2 in the Fenton reaction and the overall efficiency of the photo-Fenton process. Ferric speciation diagrams, including the ferric hydroxide complexes, antibiotic species and their interaction with ferric ions, showed the formation of those strong Fe(III)-antibiotic complexes. Process intensification of the photo-Fenton reaction with ferrioxalate complexes was able to reduce the formation of those Fe(III)-antibiotic complexes, enhancing the reaction efficiency at near neutral pH values (5.0) and using low iron concentration (5.0 mg/L). Ferrioxalate complexes are stronger than Fe(III)-antibiotic complexes, improving the quantum yield for ferrous ions production. The efficiency of the photo-Fenton reaction was also compared with the heterogeneous photocatalysis (TiO2/UV and TiO2/H2O2/UV), driven by natural solar radiation using photoreactors with compound parabolic collectors (CPCs) at pilot scale. The speciation of antibiotics molecules in solution as a function of pH plays also an important role in the reactivity of ROS. (C) 2014 Elsevier B.V. All rights reserved.