In this study, we attempt for the first time to couple sonication and photo-Fenton for bacterial inactivation of secondary treated effluent. Synthetic wastewater was subjected to sequential high-frequency/low power sonication, followed by mild photo-Fenton treatment, under a solar simulator. It was followed by the assessment of the contribution of each component of the process (Fenton, US, hv) towards the removal rate and the long-term survival; sunlight greatly improved the treatment efficiency, with the coupled process being the only one to yield total inactivation within the 4-h period of treatment. The short-term beneficial disinfecting action of US and its detrimental effect on bacterial survival in long term, as well as the impact of light addition were also revealed. Finally, an investigation on the operational parameters of the process was performed, to investigate possible improvement and/or limitations of the coupled treatment; 3 levels of each parameter involved (hydraulic, environmental, US and Fenton) were tested. Only H2O2 increased improved the process significantly, but the action mode of the joint process indicated potential cost-effective solutions towards the implementation of this method. © 2014 Elsevier B.V. All rights reserved.