KMAN Publication Inc. Quality of Life and Health Sciences 2 Serial Number 3 2026 01 01 Fatigue and Quality of Life Among Patients With Multiple Sclerosis: The Mediating Role of Depression and the Moderating Role of Psychological Resilience Fatigue and Quality of Life Among Patients With Multiple Sclerosis: The Mediating Role of Depression and the Moderating Role of Psychological Resilience 1 15 10.61838/q662sw69 EN Journal Article 2025 09 16 <table> <tbody> <tr> <td> <p><strong>Objective:</strong> This study aimed to examine the relationship between fatigue and health-related quality of life among patients with multiple sclerosis in South Africa by testing the mediating role of depression and the moderating role of psychological resilience.</p> <p><strong>Methods and Materials: </strong>This descriptive-correlational cross-sectional study was conducted using a moderated mediation design. The study population consisted of adult patients with multiple sclerosis receiving care from neurology clinics, rehabilitation centers, and multiple sclerosis support organizations in South Africa. A total of 312 patients were selected through purposive convenience sampling. Data were collected using a demographic and clinical information form, the Modified Fatigue Impact Scale, the Multiple Sclerosis Quality of Life-54 questionnaire, the Beck Depression Inventory-II, and the Connor-Davidson Resilience Scale. Data were analyzed using descriptive statistics, Pearson correlation coefficients, regression-based mediation analysis, moderation analysis, and bootstrap procedures with 5,000 resamples. Statistical significance was considered at p &lt; .05.</p> <p><strong>Findings: </strong>Inferential findings showed that fatigue was positively associated with depression and negatively associated with physical, mental, and overall health-related quality of life. Depression was negatively associated with overall quality of life, while psychological resilience was positively associated with quality of life. Fatigue significantly predicted depression (B = 0.408, β = .61, p &lt; .001) and overall quality of life (B = -0.442, β = -.40, p &lt; .001). Depression significantly mediated the relationship between fatigue and overall quality of life, with a significant indirect effect of -0.290 and a 95% confidence interval of [-0.386, -0.211]. Psychological resilience significantly moderated the association between depression and quality of life (B = 0.014, β = .16, p = .001), and the index of moderated mediation was significant (0.006, 95% CI [0.002, 0.010]).</p> <p><strong>Conclusion: </strong>The findings indicate that fatigue reduces quality of life among patients with multiple sclerosis both directly and indirectly through depression, while psychological resilience buffers the negative effect of depression on quality of life.</p> </td> </tr> </tbody> </table> https://journals.kmanpub.com/index.php/qlhs/article/download/5776/10969