Objective: To investigate the potential of 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) as a biomarker for disease activity and oxidative stress in the CSF of patients with multiple sclerosis (MS). Methods: The isoprostane 8-iso-PGF 2α is an established biomarker for in vivo oxidative stress and lipid peroxidation. We measured CSF 8-isoPGF 2α levels in 231 patients with MS (74 with relapsing-remitting MS, 67 with primary progressive MS, and 90 with secondary progressive MS [SPMS]) and 40 controls using a competition ELISA. Results: We found increased CSF levels of 8-iso-PGF 2α in patients with MS compared to controls, with the most striking values in a subgroup of patients with SPMS. Furthermore, the increase in 8-iso-PGF 2α correlated with other parameters of lipid peroxidation as well as with a decrease in the total antioxidant status in the MS CSF samples. Conclusions: Our study demonstrates that CSF levels of 8-iso-PGF 2α may serve as a biomarker of oxidative stress in MS. Further investigation will help establish the pathologic and clinical significance of our preliminary findings.