BackgroundChronic physical illness increases the risk of subsequent depressive symptoms, but we know little about the mechanisms underlying this association that interventions can target. We investigated whether loneliness might explain associations between chronic illness and subsequent depressive symptoms. MethodsWe used English Longitudinal Study of Ageing data, a prospective cohort of adults over 50. Our exposure was chronic illnesses (wave two) including arthritis, cancer, diabetes, cardiovascular disease, stroke, and chronic obstructive pulmonary disease. Loneliness scores were a mediator on the short University of California, Los Angeles Loneliness Scale at wave three. Depressive symptom scores (outcome) were measured using the Centre for Epidemiologic Studies Depression Scale (wave four). We examined associations of chronic physical illness with loneliness and depressive symptoms in univariable and multivariable regression models. ResultsFully-adjusted models included 2436 participants with the depression outcome and 2052 participants with the loneliness outcome. Chronic physical illness was associated with 21 % (incident rate ratio = 1.21, 95%CI = 1.03–1.42) higher depression scores at follow-up. We found no evidence of an association between chronic physical illness and loneliness and therefore did not proceed to analyses of mediation. LimitationsMore prevalent chronic illnesses could have driven our results, such as cardiovascular disease. ConclusionsChronic physical illnesses increase the risk of depressive symptoms in older adults. However, we did not find any that chronic physical illnesses were associated with an increased risk of subsequent loneliness. Therefore, interventions targeting loneliness to reduce depression in older adults with chronic physical illness may be insufficient.