In this study, a CFD modelling of a horizontal straight tube was carried out to investigate the effect of fraction of hybrid water based CuO-TiO2 nanofluid on thermal performance. In the numerical analysis, in order to ensure fully developed flow, the tested tube was adjusted, and uniform heat flux was applied on outer surface of the test tube. Different turbulence models were examined and k-ω Shear Stress Transport (SST) turbulent model was employed to simulate turbulent flow, and analyses were implemented for Reynolds number ranging from 10,000 to 50,000. The flow was simulated as a mixture model, and properties of nanoparticles and water are assumed as not depends on temperature. Thermo-physical properties of nanofluid were calculated from commonly used equations in literature. Nanofluid volume fractions (φ) in water were employed as 5, 4, 3, and 2% in which each concentration has different volume fractions of CuO and TiO2. As a result, the higher volume concentration of CuO compared to TiO2, the higher heat transfer coefficient was obtained. However, the highest effective Nusselt number of 1.145 is obtained for volume fraction of CuO and TiO2 is 0.02 and 0.03, respectively at Reynolds number of 50,000.