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Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Previous studies showed that perceived social support has an important role in enhancing patient's quality of life (QOL). However, the precise mechanisms through which social support exerts such an effect are not completely understood. The aim of this paper is to test two alternative models explaining the relationship between social support (positive and problematic) and two dimensions of QOL: Health-Related (HR-QOL) and Non-Health-Related (NHR-QOL).Design: Model A (mediation) hypothesized that positive support would reduce stress while problematic support would increase stress), and that this in turn would reduce QOL. Model B (moderation) hypothesized that the effect of support on QOL would be moderated by the experience of stress in that more stressed individuals would show stronger effects.Methods: Three hundred and forty-four Italian patients with SLE completed an online questionnaire.Results: Stress partially mediated the relationship between support and QOL dimensions (either HR-QOL and NHR-QOL) thus supporting Model B. As hypothesized, positive support reduced stress, while problematic support increased stress.Conclusions: These findings help to explain the complex relationship between social support, stress and QOL in patients with SLE. [ABSTRACT FROM AUTHOR]