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Quality of Life (QOL) is reported to be lower for patients with depression than the general population. This study aims to investigate the mediational effects of protective resource factors (PSFs), such as depressive symptom management ability, self-efficacy, social support and problem-focused coping act, in the relationship between dysfunctional attitudes and QOL. It is hypothesized that these PSFs have different mediating strengths. Self-report questionnaires which aimed to determine the influences of these PSFs through a multiple mediation framework were completed by 80 depressed adult outpatients from the National University Hospital of Singapore. PSFs have different influence on mental and physical QOL. Depressive symptom management ability is the most important PSF mediating both domains and better problem-focused coping abilities demonstrate improvement in the physical domain of QOL. Self-efficacy and social support are shown to be non-significant mediators. The results suggest for future effective interventions to focus primarily on improving depression patients' symptom management ability and problem-focused coping skills to raise their life quality. Furthermore, findings from this study have implications on the future investigation of QOL as a unitary construct., (Copyright © 2015 Elsevier B.V. All rights reserved.)