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The cooling system of a Class 8 truck engine was modeled using the Flowmaster computer code. Numerical simulations were performed replacing the standard coolant, 50/50 mixture of ethylene-glycol and water, with nanofluids comprised of CuO nanoparticles suspended in a base fluid of a 50/50 mixture of ethylene-glycol and water. By using engine and cooling system parameters from the standard coolant case, the higher heat transfer coefficients of the nanofluids resulted in lower engine and coolant temperatures. These temperature reductions introduced flexibility in system parameters - three of which were investigated for performance improvement: engine power, coolant pump speed and power, and radiator air-side area.