AbstractBackground and ObjectivesThe ubiquity of multimorbidity makes it crucial to examine the intermediary factors linking it with quality of life (QoL). The objective was to examine to what extent the association between multimorbidity and QoL was mediated by functional and emotional/mental health and how these mediation pathways differed by sociodemographic factors (age, gender, education, and financial strain).Research Design and MethodsData from Waves 4 to 8 of 36,908 individuals from the Survey of Health, Aging, and Retirement in Europe (SHARE) were included. Multimorbidity (exposure) was defined as having 2 or more chronic conditions. Mediators included limitations with (instrumental) activities of daily living (ADL and IADL), loneliness, and depressive symptoms. QoL (outcome) was assessed with the CASP-12 scale. Longitudinal model-based causal mediation analyses were performed to decompose the total association between multimorbidity and QoL into direct and indirect effects. Moderated mediation analyses tested for differences in mediation pathways by sociodemographic factors.ResultsMultimorbidity was significantly associated with lower QoL (direct effect:b= −0.66). This association was mediated by ADL limitations (percentage mediated 0.97%), IADL limitations (3.24%), and depressive symptoms (16.70%), but not by loneliness. The mediation pathways were moderated by age, education, financial strain, and gender.Discussion and ImplicationsADL, IADL, and depressive symptoms are crucial intermediary factors between multimorbidity and QoL in older European adults, with changing importance according to age, education, financial strain, and gender. The findings may help to increase the QoL of individuals with multimorbidity and redirect care efforts to these factors.