BACKGROUND: Research has suggested that exposure to loneliness can have a powerful detrimental impact on health, including mental health. Addressing socially determined health inequity requires understanding of the situation of marginalized or vulnerable groups. People with disability are increasingly being recognized as one such group. Little population-based research has addressed the association between loneliness and health among working age adults with and without disability. METHODS: Secondary analysis of data collected in waves 8 and 9 of Understanding Society, the UK's main annual household panel study. RESULTS: Rates of exposure to substantial loneliness were 25.4% (95%CI 23.5-27.3%) among adults with persistent disability (disability at W8 and W9), 15.4% (13.3-17.5%) among adults with disability onset (disability at W9 only), 12.3% (10.1-14.5%) among adults with disability offset (disability at W8 only), and 6.9% (6.5-7.3%) among adults with no disability. Exposure to loneliness was positively associated with the incidence (GHQ-12) and prevalence (SF-12 Mental) of mental health problems, but not the prevalence of physical health problems (SF-12 Physical). Disability status appeared to moderate the association between loneliness and health, with the difference between the persistent disability and no disability group increasing with exposure to greater levels of loneliness. CONCLUSION: Loneliness may be an important determinant of the poorer mental health of working age adults with disability in the UK. Exposure rates are significantly higher than among the non-disabled population. The strength of association between exposure to loneliness and poorer mental health is greater for people with persistent disability than people with no disability. © The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.