Abstract-Little is known about how the symptoms experienced by individuals with serious mental illness (SMI) affect family relationships. This study assessed the association between symptoms and patient perceptions of family relationships. The sample of 226 outpatient Veterans diagnosed with SMI, whose relatives had low contact rates with treatment staff, was enrolled in a study that used shared decision making to consider family involvement in care. We analyzed baseline data using multiple regressions to understand the unique effect that positive, negative, and depressive symptoms have on perceptions of family relationships, including general functioning, problem solving, communication, support, satisfaction, conflict, and distress. Greater depressive and disorganized symptoms were significant, unique predictors of perceptions of poorer communication and problem solving, while higher levels of expressive negative symptoms-blunted affect, lack of spontaneity, and motor retardation-were unique predictors of better communication and problem solving. More depressive symptoms also significantly predicted perceptions of greater family conflict and distress. While we cannot assume causation, these associations underscore the important role of depression and expressive negative symptoms in adopting a family-centered approach in the care of persons with SMI.Clinical Trial Registration: ClinicalTrials.gov: "The effectiveness of FMPO in improving the quality of care for persons with severe mental illness"; NCT00466323; https://clinicaltrials.gov/ct2/show/NCT00466323