ABSTRACT Clinical relevance: Dry eye disease is a common chronic ocular condition, which is acknowledged to have adverse impacts on quality of life and work productivity. Background: The wide-reaching impacts of dry eye disease on mental health and quality of life have received growing attention in recent years. The purpose of this study was therefore to investigate the relationship between dry eye disease, self-perceived health status, and self-reported psychological stress burden. Methods: Three hundred and twelve community residents (178 females, 134 males; mean ± SD age, 38 ± 21 years) with no major systemic, ophthalmic, or psychiatric conditions (other than dry eye disease), were recruited in a cross-sectional study. Self-perceived health status and self-reported psychological stress burden were assessed, and dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session, in accordance with the global consensus recommendations of the Tear Film and Ocular Surface Society Dry Eye Workshop II reports. Results: Multivariate regression analysis, adjusted for age, sex, ethnicity, and contact lens wear, demonstrated that improved self-perceived health status was associated with decreased odds of dry eye disease, aqueous tear deficiency and meibomian gland dysfunction (all p < 0.05). Increased self-reported psychological stress burden was positively associated with dry eye disease, aqueous tear deficiency and meibomian gland dysfunction (all p ≤ 0.01). Conclusion: Dry eye disease is associated with poorer self-perceived health status and greater self-reported psychological stress burden. The findings of this study highlight the wide-reaching impacts of dry eye disease, and the importance of minimising the impacts of the condition with optimised management and actioning inter-disciplinary referral for affected patients where necessary.