In this study, numerical simulation was used to investigate the effect of adding different nano-particles into the fluid on the performance of a baffled shell-and-tube heat exchanger. A three-dimensional modeling approach was followed to analyze the effect of different nano-fluids, at various volume fractions, as applied in a baffled shell-and-tube heat exchanger. Once finished with validating the grid independency and results, we proceeded to obtain heat transfer rate, pressure drop, outlet shell temperature and exchanger effectiveness for different volume fractions and particle size of different nanofluids. The studied nano-particles in the present work included Al2O3, CuO, Fe2O3, Cu, Fe, SiO2, and Au, with water and ethylene glycol employed as base fluids. With constant mass flow rate for all cases, the results indicated that, the addition of nano-particles had reduced the heat transfer coefficient, pressure drop and the rate of heat transfer through the shell, even though it had increased outlet shell temperature. In other words, considering a constant heat transfer rate, the presence of nanofluids in a baffled shell-and-tube heat exchanger is likely to be associated with increased outlet shell temperature. Another consequence presents that using ethylene glycol as base fluid leads to higher effectiveness compared with water as a base fluid in exchanger.