Objective: The purpose of this study was to investigate the levels of non-esterified fatty acids in plasma from patients with multiple sclerosis and further to correlate these findings with the neurological profile as measured by the Kurtzke Expanded Disability Status Scale. Methods: Plasma non-esterified fatty acids and esterified fatty acids from 30 control subjects and 31 patients with multiple sclerosis were measured by gas chromatography. Results: Non-esterified fatty acids C18:2n-6, C20:4n-6, C16:1n-7, C18:1n-7, C18:1n-9, C14:0, C16:0 and C18:0 were significantly increased in plasma from patients with multiple sclerosis, P ≤ 0.01, while esterified fatty acid C18:2n-6 was decreased, P = 0.003. Fatty acid PC C16:1n-7 and non-esterified fatty acids C16:1n-7, C18:1n-7 and C18:1n-9 showed positive and fatty acids C18:1n-9, C20:0, C22:0 and C24:0 showed inverse correlations with the Functional System Scores. Conclusions: We have identified increased monounsaturated non-esterified fatty acids in plasma from patients with multiple sclerosis as indicative of a worse disease outcome. Further, the decrease in fatty acid C18:2n-6, with increases in non-esterified fatty acids C18:2n-6 and C20:4n-6, suggested a role for these eicosanoid precursor fatty acids in the inflammatory condition experienced by these patients.