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In this work, a three-dimensional analysis is used to study the heat transfer performance of nanofluid flows through a flattened tube in a laminar flow regime and constant heat flux boundary condition. CuO nanoparticles dispersed in ethylene glycol with particle volume concentrations ranging between 0 and 4vol.% were used as working fluids for simulating the heat transfer of nanofluids. Effects of some important parameters such as nanoparticle volume concentration, particles Brownian motions, and Reynolds number on heat transfer coefficient have been determined and discussed in details. Results have shown that the heat transfer coefficient increases with increase in the volume concentration level of the nanoparticle, Brownian motion and the Reynolds number. Numerical results have been validated by comparison of simulations with those available in the literature.