||Multiple sclerosis (MS) is a neurologic autoimmune disease, which is the leading cause of nontraumatic neurologic disability in young adults in United States and Europe. n-3 polyunsaturated fatty acids (PUFA) are reported to mitigate severity of this disease. Recent studies suggest that phospholipid (PL) form of dietary n-3 PUFA may lead to their higher tissue accretion than triacylglycerol (TAG) form. We compared efficacy of PL-docosahexaenoic acid (22:6n-3) (DHA) and TAG-DHA on onset and severity of experimental autoimmune encephalomyelitis (EAE) in a mouse model of MS. Female mice were fed low alpha-linolenic acid (18:3n-3) (ALA) diet (control) for 2 weeks and then fed either control, 0.3%, or 1.0% DHA (PL or TAG) for 4 weeks pre-EAE induction and 4 weeks post-EAE induction. The brain and spinal cord n-6:n-3 ratio was significantly lower in all mice fed DHA compared to control. EAE onset was delayed in mice fed both DHA forms and concentrations, except for 1% TAG-DHA. The inverse association between the EAE score and the brain DHA concentration was nonsignificant at the end of the study (p = 0.08). Daily EAE scores of mice fed different DHA diets did not differ from control, however, the score of all DHA groups combined during days 9-16 was lower (p = 0.028) compared to the control. During days 17-22, the EAE score trended lower in 0.3% TAG-DHA and during days 23-28, the EAE score trended lower in both PL-DHA groups than those in all other groups. These findings suggest that TAG-DHA may be more effective than PL-DHA in the early phases of EAE, and in the final outcome, PL-DHA may be more effective than TAG-DHA. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.