Abnormal metabolism of essential polyunsaturated fatty acids (EPUFAs), a component of phospholipids in neural membranes, has been suggested to be related to the pathophysiology of schizophrenia. The purpose of this study was to examine the relationship between EPUFA concentrations in erythrocyte membranes, a peripheral measure of phospholipid composition in the brain, and clinical variables, such as cognitive performance relevant to social functions, in patients with schizophrenia. Erythrocyte membrane levels of EPUFAs, saturated fatty acids, and monounsaturated acids were measured in 25 patients with schizophrenia and 32 age- and gender-matched 32 normal volunteers. The script tasks, a measure of social cognition, and the Brief Psychiatric Rating Scale were administered to the patients. The levels of EPUFAs, but not those of saturated or monosaturated fatty acids, were significantly lower in patients than in normal controls. The degree of a decrease in EPUFA levels was positively correlated with severity of positive symptoms and impairment of frequency judgment performance on the script tasks, while no such correlations were found with negative symptoms, attention as measured by the Wechsler Adult Intelligence Scale-Revised-Digit Span, or verbal memory as measured by the Auditory Verbal Learning Test. These results provide the first suggestion for a contribution of decreased levels of EPUFAs to impaired social cognition, as represented by event schema, in patients with schizophrenia.