This paper presents a transient investigation on the performance of a solar desiccant cooling system integrated with a counter flow Maisotsenko cycle heat and mass exchanger as an air-conditioning system for the buildings in hot and humid areas. The investigation is performed using TRNSYS software linked with a MALAB code for simulating the Maisotsenko cycle. The developed model is validated using the experimental data with the highest deviation of 4.5%. Three different mixtures of the indoor and outdoor air [100%:0% (RA1), 75%:25% (RA2) and 50%:50% (RA3)] are considered as the return air. It is found that the COP and the cooling capacity of the system decrease by the more fraction of outdoor air in the return air, whereas the supply and regeneration temperatures increase. The findings show that the solar fraction in the case of RA1 is approximately half that in the case of RA3. Based on the results of the sensitivity analysis of the system with 100% indoor air as return air, the system EER increases slightly from 0.78 to 0.82 by increasing the collector area from 16 to 25 m2. However, the system COP has a reducing trend by the collector area. Both COP and EER are enhanced by the heat wheel efficiency, because the more sensible load from the supply air is transferred to the return air.