Energy and exergy (EnE) efficiencies are considered the most important parameters to compare the performance of various thermal systems. In this paper, an analysis was carried out for EnE efficiencies of a flat plate solar collector (FPSC) using four different kinds of nanofluids as flowing mediums, namely, Al2O3/water, MgO/water, TiO2/water, and CuO/water, and compared with water as a flowing medium (traditional base fluid). The analysis considered nanofluids made of nanomaterials’ volume fractions of 1−4% with water. The volume flow rates of nanofluids and water were 1 to 4 L/min. The solar collector′s highest EnE efficiency values were obtained for CuO/water nanofluid among the four types of nanofluids mentioned above. The EnE efficiencies of the CuO nanofluid-operated solar collector were 38.21% and 34.06%, respectively, which is significantly higher than that of water-operated solar collectors. For the same volume flow rate, the mass flow rate was found to be 15.95% higher than water for the CuO nanofluid. The EnE efficiency of FPSC can also be increased by increasing the density and reducing the specific heat of the flowing medium.