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Purpose This paper aims to investigate the three-dimensional (3D) numerical simulations, based on the Navier–Stokes equations and the energy equation. Forced convection of a mixture of (60:40) percent ethylene glycol and water, was used as the base fluid and CuO nanoparticles, through a serpentine minichannel. Design/methodology/approach In this simulation, a serpentine mini-channel heat exchanger was simulated. The fluid studied in this simulation was composed of a mixture of (60:40) per cent ethylene glycol and water, was used as the base fluid and CuO nanoparticles. Four slabs and three serpentines were used in this study. The serpentine section is connected to the slab. Three equidistant circular channels (1 mm in diameter) were implemented inside the slab. Findings Results show that nanoparticles increase the fluid pressure drop and by changing volume fraction of nanoparticles from 0 to 1 per cent, the pressure drop of nanofluids increases between 42and 47 per cent, for Reynolds numbers from 100 to 500. The existence of serpentine bend in the minichannel heat exchanger causes the heat transfer rate to increase. Increase the volume fraction of nanoparticles reduces the fluid temperature at the outlet of the heat exchanger. The numerical results show that in Re = 500, at the beginning of the last slab in middle channel by changing volume fraction of nanoparticles from 0 to 2 per cent, local Nusselt number 57.40 per cent increase. The existence of the serpentine bend causes the heat transfer rate to increase. Originality/value Forced convection of a mixture of (60:40) per cent ethylene glycol and water by using of 3D numerical simulations, based on the Navier–Stokes equations.