The purpose of this research is to investigate the annual operating energy performance of a desiccant and evaporative-cooling-assisted 100% outdoor air system. The seasonal mode of operation of the proposed system is also suggested and used for estimating the energy saving potentials. The TRNSYS 16 program integrated with a commercial equation solver is used for the energy simulation of the proposed system, and then two existing air handling alternatives: a conventional variable air volume (VAV) system and an existing evaporative-cooling-assisted system are compared with the proposed system. The proposed system shows operating energy savings of 82% over the conventional VAV system during the summer, and 54% and 37% in the winter and the intermediate season operations, respectively. Ultimately, the proposed system provides 68% annual operating energy saving over the conventional VAV system, and 23% savings compared to the established evaporative-cooling-assisted system. It is also found that the extreme energy benefit can be obtained by enhancing the evaporative cooling effects using the liquid desiccant (LD) unit. The operating energy saving of the LD unit can be achieved by applying the water-side free cooling and the solar thermal system. (C) 2014 Elsevier B.V. All rights reserved.