This work was to investigate the interactions of Cu NPs with dispersant, detergent, antioxidant, friction modifier, viscosity index improver on tribological performance and some physicochemical properties of diisooctylsebacate (DIOS). The results indicate that Cu NPs and most additives have a synergy on tribological performance. Whereas, Cu NPs and dispersant or detergent can only enhance wear resistance. When phenols antioxidant, viscosity index improver and ZDDP are added together with Cu NPs, the antioxidation performance of DIOS can be distinctly improved. Nevertheless, amines antioxidant and Cu NPs exhibit antagonistic effect. The kinematic viscosity of DIOS can be enhanced by adding viscosity index improver together with Cu NPs. The synergetic effects between ZDDP/MoDTC and Cu NPs are both obvious in many properties.