In this paper, the effect of multilayer screen mesh wicks and CuO nano-fluid as working fluid is investigated on the performance of heat pipe. Three heat pipes were fabricated with different layers of screen mesh wicks to improve capillary action of working fluid. Heat pipes of 350 mm length and 19.5 mm diameter were used. The different mesh configurations used in this work were 100+150 mesh, 100+2X150 mesh and 4X150 meshes. The concentration of CuO nano-fluids in the experiments was maintained at 1% by weight of water. The heat pipes are tested with water and CuO as working fluid for different heat inputs of 35W, 50W 75W, 100W and 120W. The thermal resistance and heat transfer rate were determined. It is found that the thermal resistance decreases with increase in heat input. There is increase in heat transfer rate in case of CuO nanofluid loading in ordinary water compared to distilled water as working fluid. For all orientation the maximum heat transfer through the heat pipe increased as the number of mesh layer of the wick is increased. The heat transfer rate is found to be maximum at 100 l/h mass flow rate compared to that of 150 l/h.