This paper presents performance definitions for calculating the overall effectiveness of three-fluid heat and moisture exchangers. The three-fluid heat and moisture exchanger considered in this paper is a combination of a liquid-to-liquid heat exchanger for heat transfer between a desiccant solution and a refrigerant and an energy exchanger for heat and moisture transfer between desiccant solution and air streams. The performance definitions presented in this paper are used to calculate the overall sensible and latent effectivenesses of a three-fluid heat and moisture exchanger, which has been tested under air cooling and dehumidifying operating conditions in a previous work (Abdel-Salam et al., 2016, “Design and Testing of a Novel 3-Fluid Liquid-to-Air Membrane Energy Exchanger (3-Fluid LAMEE),” Int. J. Heat Mass Transfer, 92, pp. 312–329). The effectiveness of this three-fluid heat and moisture exchanger is compared when calculated using the traditional energy exchanger effectiveness equations and the overall performance definitions. Results show that the overall performance definitions provide effectiveness values that are less sensitive to changes in the inlet refrigerant temperature and therefore are more generally applicable for energy exchanger design than the traditional effectiveness equations used in the literature.