Wear particle-induced biological responses are the major factors for the failure of total joint arthroplasties, but it is possible to improve the lubrication and reduce the wear of an artificial joint system. Polyetheretherketone (PEEK), with ultra-high molecular weight polyethylene, is a suitable bearing material due to its resistance to fatigue strain. However, the effects of major compositions of synovial fluid on the wear of PEEK are unclear. We characterized the effects of three major components of synovial fluid including albumin, globulin, and phospholipids on the morphology and wear rate of PEEK wear particles. Our results demonstrated that the concentrations of albumin and globulin could affect the morphology of PEEK wear particles. In addition, a higher concentration of globulin and phospholipids (12.5 mg/mL) resulted in an increase in the amount of wear particles by 2.8-and 1.7-fold, respectively. In contrast, increasing albumin caused a reduction of wear particle numbers. These results indicate increasing concentration of albumin or reducing concentration of globulin or phospholipids has a better effect on reducing the numbers of wear particles and provides a potential solution of reducing PEEK wear particles, thus it can be more effectively applied in other biomedical systems.