Friction and wear reduction are urgently sought to promote energy savings and performance of precision manufacturing equipment. The molecular dynamics (MD) simulation unveils the detailed lubrication mechanisms of the particle size effect of single Cu NPs and the size synergy effect of multiple Cu NPs. By setting various particle sizes and quantities, the tribological properties of the lubrication system under multiple complex conditions are compared. The stress, strain, wear volume, friction force, normal force, and temperature at the fluid-solid boundary are quantitatively calculated. The results indicate that the average values of friction force are maximally reduced approximately 83.65 %, the wear rate is maximally decreased 22.5 %, the max stress is maximally reduced 22.46 % and the peak temp is maximally reduced 8 % after the addition of Cu NPs. The tribological properties improves as particle size increases, but there is an optimal Cu NP size that yields the best tribological properties. In addition, the tribological properties of the multiple particles are superior to those of the single particle. The results indicate that small and uniform Cu NPs show superior tribological properties over dispersed sizes, small Cu NPs can contribute to improve the overall tribological properties of the system primarily comprises large Cu NPs.