The purpose of this study is to analyze the influence of using air cooling desiccant systems on reaching thermal comfort conditions in the interior of a building, supposing this to be an open system. Exergy analysis has been carried out for the different design temperatures and relative humidity conditions within those established for ASHRAE summer thermal comfort conditions. The climatic conditions of a hot humid climate such as Villahermosa, Tabasco, Mexico, are used as an example. A novel reference state has been used for the exergy analysis, since this varies according to the fluctuation of the ambient temperature and humidity.