Loneliness, Social Isolation, and Chronic Disease Outcomes in Adults: A Systematic Review

Social disconnection, including loneliness and social isolation, is increasingly recognized as an important social determinant of adult health, but its relationship with chronic disease-related outcomes remains dispersed across disease areas and study designs. This systematic review aimed to synthesize evidence on the associations of loneliness and social isolation with chronic disease-related outcomes among adults in community, primary care, outpatient, registry-based, and population-based settings. PubMed/MEDLINE, Scopus, Web of Science, Web of Science East Mediterranean Region, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, the Cochrane Library, Google Scholar, and reference lists were searched from database inception to May 10, 2026, for original studies reporting loneliness or social isolation in relation to cardiovascular, metabolic, respiratory, renal, frailty-related, behavioral, biological, functional, quality-of-life, morbidity, or mortality outcomes. Thirty-one studies were included and synthesized narratively because of heterogeneity in populations, exposure measures, outcomes, study designs, follow-up periods, adjustment strategies, and reported effect estimates. The included evidence was mainly observational and suggested associations between loneliness, social isolation, and a broad range of adverse chronic disease-related outcomes, with more consistent associations reported for cardiovascular disease, cardiometabolic conditions, chronic kidney disease, frailty, functional impairment, and mortality. Behavioral pathways, reduced self-management, poorer preventive behavior, lower medication adherence, and inflammatory mechanisms may partly explain these associations, although causal inference remains limited. Loneliness and social isolation appeared related but not interchangeable, as both reflect social disconnection, although loneliness is subjective, while social isolation is more objective and structural. These findings support further evaluation of social disconnection assessment in adults with or at risk of chronic disease, particularly in primary care and outpatient settings. Future research should use standardized exposure measures, repeated assessment, and stronger longitudinal, registry-linked, or intervention designs to clarify temporal directionality and determine whether improving social connection can improve chronic disease outcomes.