Objective To investigate the sequential mediation effects of pain and activities of daily living (ADLs) on the relationship between multimorbidity and depressive symptoms among middle-aged and older adults in rural China, providing evidence to optimize health management strategies.

Methods Using four waves of data (2011–2018) from the China Health and Retirement Longitudinal Study (CHARLS), cross-sectional logistic models and panel random-effects models were used to examine the associations and effects of multimorbidity, pain, ADLs, and depression. Structural equation modeling (SEM) combined with the Bootstrap method was applied to analyze the mediation pathways.

Results A total of 2949 middle-aged and older participants were included in the study. When instrumental activities of dailyliving (IADLs) were used as the mediator, approximately 48.44% of the association between comorbidity and depression was attributable to the mediating path of physical pain and IADLs (0.051, 95% CI: 0.045–0.056). When basic activities of daily living (BADLs) were used as the mediator, approximately 47.91% of the association between comorbidity and depression was attributable to the mediating path of physical pain and BADLs (0.050, 95% CI: 0.045–0.056). The chain mediating pathways involving physical pain and the development of daily living abilities were both statistically significant (0.005, 95% CI: 0.004–0.006).

Conclusion Multimorbidity directly increases the risk of depression and also exacerbates this risk through pain and subsequent declines in ADLs, either independently or sequentially.