In this study, the effects of using pure water and Zinc oxide/water nanofluid as working fluids on the performance of a photovoltaic thermal system are evaluated using computational fluid dynamic approach. Moreover, effects of the parameters that are independent of the system design on the electrical and thermal efficiencies of the photovoltaic thermal system with Zinc oxide/water nanofluid are investigated. The studied parameters are: absorbed solar irradiation, wind speed, ambient temperature, coolant inlet temperature, coolant mass flow rate, and nanoparticles mass fraction in the Zinc oxide/water nanofluid. In this study, using the designed setup, the three-dimensional numerical model is validated by comparing the simulation results with those of the experiments. The experiments are performed on a selected day in August at the Ferdowsi University of Mashhad, Mashhad, Iran (Latitude: 36° and Longitude: 59°). Based on the numerical results, the thermal efficiency of the photovoltaic thermal system with Zinc oxide/water nanofluid is enhanced by increasing the absorbed solar irradiation, ambient temperature, coolant mass flow rate, and nanoparticles mass fraction. However, increasing the wind speed and coolant inlet temperature decreases the thermal efficiency of the system. Moreover, the considered parameters in this study have slight effects on the electrical efficiency of the photovoltaic thermal system. The relative increase of the electrical and thermal efficiencies of the photovoltaic thermal system with Zinc oxide/water nanofluid with 12 % by weight compared to that of pure water is 0.28 % and 12.58 %, respectively.