Progressive supranuclear palsy (PSP) is a neurodegenerative disorder, which may possibly be induced by oxidative stress. However, the age-related alteration of the endogenous antioxidant system is not well understood. To better understand this, we measured Cu/Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx), and 4-hydroxynonenal (HNE)-conjugated GPx in cerebrospinal fluid of PSP patients by enzyme linked immunosorbent assay. A significant increase in the Cu/Zn-SOD level was detected in PSP group compared with controls. The levels of Cu/Zn-SOD and GPx in PSP group showed positive correlations with age. Two-thirds of total GPx was present as the HNE-conjugated form with positive correlation in PSP group. In conclusion, the endogenous antioxidant system of PSP patients appears to be activated with aging, however, it might be unable to function effectively because of conjugation with HNE.