Deficiency in long-chain omega-3 (LCn - 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n - 3) and docosahexaenoic acid (DHA, 22:6n - 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DHA levels in adult medication-free patients SZ (n=20) and age-matched healthy controls (n=24). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, -22%, P=0.007). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square, P=0.001). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4n-6) (+9%, P=0.02) and the AA:EPA + DHA ratio (+28%, P=0.0004) were significantly greater in SZ patients. Linoleic acid (18:2n-6) was significantly lower (-12%, P=0.009) and the erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was significantly elevated in SZ patients. Compared with same-gender controls, EPA + DHA composition was significantly lower in male (-19%, P=0.04) but not female (-13%, P=0.33) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%, P=0.008) and female (+22%, P=0.04) SZ patients. These results suggest that the majority of SZ patients exhibit low LCn - 3 fatty acid levels which may place them at increased risk for cardiovascular morbidity and mortality. Copyright © 2013 Robert K. McNamara et al.