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Background: Given the well-established association between perceived stress and quality of life (QoL) in dementia patients and their partners, our goal was to identify whether relationship quality and dyadic coping would operate as mediators between perceived stress and QoL. Results: We found negative correlations between stress and QoL in both partners (QoL-AD: r = -0.62; p < 0.001; WHO-QOL Overall: r = -0.27; p = 0.02). Spousal caregivers had a significantly lower DCI total score than dementia patients (p < 0.001). Dyadic coping was a significant mediator of the relationship between stress and QoL in spousal caregivers (z = 0.28; p = 0.02), but not in dementia patients. Likewise, relationship quality significantly mediated the relationship between stress and QoL in caregivers only (z = -2.41; p = 0.02). Conclusions: This study identified dyadic coping as a mediator on the relationship between stress and QoL in (caregiving) partners of dementia patients. In patients, however, we found a direct negative effect of stress on QoL. The findings suggest the importance of stress reducing and dyadic interventions for dementia patients and their partners, respectively.