In this study, we investigated whether the siblings of patients with schizophrenia have deficits in cognition and psychosocial functioning and whether the psychosocial functioning and cognitive deficits correlate with the methylation status of the membrane-bound catechol-O-methyltransferase (MB-COMT) gene in peripheral leukocytes. Cognitive abilities were evaluated using the attention/vigilance Continuous Performance Test, delayed/immediate recall scores, the Wisconsin Card Sorting Test, and the Semantic Verbal Fluency Test. Psychosocial functioning was evaluated using the Scale for the Assessment of Negative Symptoms, the Global Assessment of Functioning scale, and the Social Adjustment Scale. A bisulfate-based sequencing was adopted to analyze the methylation status of the MB-COMT promoter in peripheral leukocytes. Significant impairments in attention/vigilance and verbal memory and significant decreases in immediate and delayed recall scores were observed in the siblings of patients with schizophrenia compared with the healthy subjects. In addition, significant deficits in global social functioning and in social interaction were found in the siblings. The tested region of the MB-COMT promoter was generally unmethylated in peripheral leukocytes, without significant correlation with behavioral deficits in the siblings.Our study demonstrated that the siblings have significant deficits in cognition and psychosocial functioning, which may not be associated with MB-COMT methylation in peripheral leukocytes.