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Optic neuritis frequently occurs during the clinical course of multiple sclerosis (MS). In this condition, demyelination of the optic nerve occurs, which electrophysiologically causes a delay in P100 wave latency. Sensitive cholesterol homeostasis is critical for the formation of the myelin sheath and for myelin to become functionally mature. High-density lipoprotein (HDL) becomes dysfunctional under oxidative stress and plays an important role in the pathogenesis of MS. In this study, HDL levels of MS patients suffering from optic neuritis were compared with those of healthy individuals, and the relationship between pattern reversal visual evoked potential (PRVEP) P100 wave latency and HDL levels in patients with optic neuritis attacks was analyzed. PRVEP studies were performed in patients with MS who had an episode of optic neuritis, and P100 wave latencies were measured. Peripheral blood samples were collected from healthy participants and patients. Lipid levels and myeloperoxidase (MPO) and paraoxonase (PON) activities were measured, and the MPO/PON ratio was then calculated. The lipid profiles and dysfunctional HDL levels in the healthy and patient groups were compared. Finally, the relationship between these parameters and the PRVEP-P100 wave latency was examined. Total cholesterol and low-density lipoprotein (LDL) levels were significantly higher in the patient group (P = .044; P = .038, respectively). There was no statistically significant difference in HDL levels between groups (P = .659). The distribution of MPO values was similar between groups (P = .452). PON values were significantly lower, whereas the MPO/PON ratios were significantly higher in the patient group than in the control group (P = .025; P = .028, respectively). A statistically significant positive correlation was found between the elevated MPO/PON ratio, representing dysfunctional HDL, and both the mean and maximum PRVEP-P100 wave latencies (P < .001, R = 0.690; P < .001, R = 0.815, respectively). A dysfunctional form of HDL may lead to poor deactivation of remyelination-limiting factors and may ultimately be associated with poor outcomes in optic neuritis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)