BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses. HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses. ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November 2010 and March 2022. METHODS: Case-control study using biobanked samples was performed and commercial competitive ELISA kit (Highly Sensitive 8-OHdG Check ELISA) utilized. Concentration of 8-OHdG was quantitated in both CSF and serum and compared between groups. RESULTS: No correlation was established between the measures of 8-OHdG in serum and CSF and group. CSF median [8-OHdG] for NAD/DM was 169.9 pg/mL (IQR : 67.18-210.6), CVSM 157.1 pg/mL (IQR : 132.1-229.1), EPM 131.4 pg/mL (IQR : 102.1-193.2), and control 149.8 pg/mL (IQR : 113.3-196.4). Serum median [8-OHdG] for NAD/DM was 130 pg/mL (IQR : 51.73-157.2), CVSM 125.8 pg/mL (IQR : 62.8-170.8), EPM 120.6 pg/mL (IQR : 87.23-229.7), and control 157.6 pg/mL (IQR : 97.15-245.6). Poisson regression analysis showed no difference established once confounding variables were considered. CONCLUSIONS: Eight-OHdG did not aid in antemortem diagnosis of NAD/DM in this cohort of horses. At the time of diagnosis horses with NAD/DM do not have ongoing oxidative stress.