Polyunsaturated fatty acid (PUFA) levels are altered in adults with cognitive decline and also depression. Depression facilitates progression from mild cognitive impairment (MCI) to dementia. We investigated associations between omega-3 (n-3) and omega-6 (n-6) PUFAs and cognition, memory and depression in 50 adults ≥65 years with MCI and 29 controls. Memory, depressive symptoms and erythrocyte PUFAs (% total fatty acids) were assessed. Eicosapentaenoic acid (EPA) was lower in MCI vs controls (.94% vs 1.26%, p<01); n-6 PUFAs were higher: dihomo-gamma-linolenic acid (1.51% vs 1.32%, p<01), arachidonic acid (11.54% vs 10.70%, p<01), n-6 docosapentaenoic acid (DPA:.46% vs.34%, p<01), and total n-6 PUFA (24.14% vs 23.37%, p<05). Higher n-6 DPA predicted poorer mental health. Lower n-3 DPA was associated with higher self-reported bodily pain. Adults with MCI had higher depression scores (3.05±39 vs 1.33±24, p<01). Depressive symptoms associated with elevated n-6 PUFA may contribute to cognitive decline in this population