["Health Expectations, Volume 29, Issue 3, June 2026. ", "\nABSTRACT\n\nBackground\nSocial isolation is a critical social determinant of health that amplifies the significant treatment burden faced by community‐dwelling adults with disabilities and multimorbidity. While an association between these factors is established, longitudinal evidence capturing their dynamic interplay is scarce, limiting the development of effective, equitable interventions. This study aimed to longitudinally explore how treatment burden evolves among this population and to elucidate the mechanisms through which social isolation appears to operate through these changes.\n\n\nMethods\nWe conducted a longitudinal qualitative study using interpretive description in Hangzhou, China. Participants were adults with physician‐diagnosed disabilities and ≥ 2 chronic conditions, recruited via purposive sampling from community health centres. Each participant completed three in‐depth, semi‐structured interviews over 12 months. We conceptualized treatment burden using Demain et al.'s adaptation of the Cumulative Complexity Model. Data analysis was an iterative process involving constant comparison to identify key themes regarding the interplay of social isolation and treatment burden over time.\n\n\nResults\nA total of 24 participants (13 were women; median age 67.5 years) completed the study. Our analysis revealed that social isolation was described by participants as dynamically contributing to increased treatment burden through four interconnected mechanisms: (1) Eroding autonomy, leading to passive healthcare decision‐making; (2) Compromising emotional well‐being, which depleted self‐management capacity; (3) Straining relational networks, resulting in the loss of crucial informal support; and (4) Creating navigational barriers, which led to difficulties managing complex treatments. A key cross‐cutting theme was the apparent role of depressive symptoms, which participants described as being exacerbated by isolation and, in turn, appearing to contribute to more negative illness perceptions and functional decline. This pattern was consistent with a progressive intensification of treatment burden as emotional and physical challenges fed into each other over time.\n\n\nConclusion\nSocial isolation appeared to function not merely as a passive correlate but as a factor that longitudinally contributed to greater treatment burden, thereby exacerbating health inequities for adults with disabilities and multimorbidity. This pattern appeared to be further shaped by the intersection with depressive symptoms. To mitigate this, multi‐level interventions are essential. Priorities should include addressing structural barriers through policies that foster community integration, strengthening mental health support within primary care, and redesigning services to be more relationally‐centred and less burdensome.\n\n\nPatient or Public Contribution\nPatients, care‐givers, people with lived experience or members of the public were not involved in the study design, conduct, data analysis or preparation of the manuscript. However, preliminary findings were shared and discussed with two patient advisors who had lived experience of disability and multimorbidity but were not participants in the interviews. Their feedback helped refine the presentation and contextual relevance of the themes.\n"]