In this study, exergy analysis of a novel desalination system is presented and discussed. The water desalination is carried out using combined humidification-dehumidification and reverse osmosis technologies. Six system performance parameters are examined: overall exergetic efficiency, equivalent electricity consumption, specific exergy destruction, specific exergy lost, and total true specific exergy lost, as well as the exergy destruction ratios of the main components. The total true specific exergy lost is a new parameter presented in this study. It is a function of summation of total the exergy destruction rate and loss per total mass flow rate of the total pure water produced. This parameter is found to be a useful parameter to assess the exergetic performance of the system considered. By contrast, use of overall exergetic efficiency as an assessment tool can result in misleading conclusions for such a desalination system and, hence, is not recommended. Furthermore, this study reveals that the highest exergy destruction occurs in the thermal vapor compressor, which accounts for 50% of the total exergy destruction of the system considered. This study, in addition, demonstrates that the specific exergy destruction of the dehumidifier and TVC are the parameters that most strongly affect the performance of the system.