<p>Chronic physical illness is a major stressor that can affect emotional health in couples. When combined with other stressors, such as the COVID-19 pandemic, well-being may be further compromised. This study examined predictors of well-being among individuals in couple relationships, considering perceived COVID-19 threat, positive dyadic coping and relationship quality. A retrospective cross-sectional design was used with 956 Portuguese partners (20.9% with a physical illness; 79.1% without). Data were collected between April 2020 and May 2021 using the Warwick-Edinburgh Well-Being Scale, the Brief Illness Perception Questionnaire, the Perceived Relationship Quality Component Inventory and the Dyadic Coping Inventory. Analyses included hierarchical regression, mediation models and qualitative comparative analysis (QCA). Linear models showed that higher perceived COVID-19 threat, poorer dyadic coping and lower relationship quality predicted lower well-being. Relationship quality mediated the association between positive dyadic coping and well-being. Non-linear models identified distinct combinations associated with well-being: high well-being was linked to low perceived COVID-19 threat and good relationship quality, whereas low well-being was associated with high perceived threat and low dyadic coping. Overall, well-being in couples is influenced by perceived COVID-19 threat, relationship quality and dyadic coping. Partner satisfaction appears central to the link between coping and psychological well-being, suggesting the importance of targeting these factors in prevention efforts for couples with or without chronic physical illness.</p>