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OBJECTIVE: Health status and disease activity in patients with systemic lupus erythematosus (SLE) and other chronic diseases are strongly associated with social support, which suggests that enhanced social support in medical care might improve SLE outcome. There has been little or no study on identifying patients for whom social support would be most beneficial. It would allow practitioners to enable social support more effectively as a complement to disease management. METHODS: A retrospective cohort (200 patients with SLE from 5 centers), balanced by race and insurance status, was studied in a cross sectional design. Demographic, clinical, socioeconomic, and psychosocial factors and disease outcomes [Systemic Lupus Activity Measure (SLAM), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR), SF-36] were measured. Using multivariate linear regression and ANOVA (outcome = SF-36 physical function, mental health), we examined the interaction between social support and patients' characteristics, including race, age, income, occupation, insurance, employment, education, and social network, and characteristics of the disease itself such as disease activity (SLAM) at diagnosis, damage (SLICC/ACR) at diagnosis, and comorbidity. RESULTS: In multivariate models, higher social support was significantly associated (p < 0.05) with better physical function when respondents were white, had income above poverty level, had Medicare or private insurance (vs Medicaid or no insurance), and had low disease activity at diagnosis. Social support was associated with better mental health, although there was no significant interaction between social support and other predictors of mental health. CONCLUSION: The data suggest that social support is beneficial for mental health for all groups, but has the greatest opportunity for influence among those already possessing social, economic, and health advantages.