Depression is a common problem among patients with multiple sclerosis (MS). Previous research has shown differences between MS patients and controls in the levels of certain fatty acids, and differences in many of these same fatty acids have also been reported in psychiatric patients with major depression. The current study sought to determine whether fatty acid levels in MS patients might be associated with depression. Fatty acids were measured in red blood cells (RBCs) for 38 patients with relapsing-remitting MS and 33 healthy controls who also completed 3-day dietary records and depression questionnaires. Levels of certain omega-3 and omega-6 fatty acids were lower and levels of certain monounsaturated and saturated fatty acids were higher in the MS patients. These differences were generally of medium effect size and occurred despite the fact that no differences were found between the two groups in dietary intake of any fatty acids. However, neither RBC nor dietary fatty acid levels were related to depression in the MS sample.