BACKGROUND: The meaning of social support is well documented, but less is known about mediating characteristics that examine which patients with end stage renal disease (ESRD) and depressive symptoms are most likely to benefit. AIMS: The aim of this study was to examine whether perceived social support mediated depressive symptoms on the outcome of quality of life (QoL). DESIGN: A correlational, cross-sectional study was conducted with a convenience sampling of 190 patients with ESRD. RESULTS: There was partial mediation effect of social support on depressive symptoms in the prediction of QoL. CONCLUSION: Effective management of depressive symptoms will improve QoL mostly when social support is promoted in patients with ESRD receiving hemodialysis.