Objectives: Research in older persons with deteriorative health shows a decrease in well-being. The aim of this study was to examine the role of psychological coping resources in the association between health decline and well-being, in a longitudinal design. Method: Data were used from the Longitudinal Aging Study Amsterdam (LASA). Health decline was defined as persistent deterioration of functioning (PDF), persistent decline in cognitive functioning and/or physical functioning, and/or increase of chronic diseases. Measurements of well-being included life satisfaction and positive affect. Measurements of coping resources included self-esteem, mastery, and self-efficacy. Results: Multivariate linear regression analyses showed that self-efficacy, mastery, and self-esteem mediated the association between PDF and change in well-being. Mastery also was a moderator of the association between PDF and life satisfaction. In older persons with a decreasing mastery, PDF was associated with a significant decrease on life satisfaction; this effect was not observed in older persons with stable or increasing mastery. Discussion: This study suggests that coping resources are of importance in explaining associations between persistent health decline and decreasing well-being. Stable or improving mastery even proves to protect older persons with PDF from decreasing well-being.Therefore, it may be of importance to develop interventions for older persons aimed at maintaining or improving psychological coping resources when health declines.