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Background: Individuals with low socioeconomic status (SES) are at a higher risk of developing depression. However, evidence on the role of cardiovascular health (CVH) in this chain is sparse and limited. The purpose of this research was to assess the mediating role of Life's Essential 8 (LE8), a recently updated measurement of CVH, in the association between SES and depression according to a nationally representative sample of adults., Methods: Data was drawn from the National Health and Nutrition Examination Survey (NHANES) in 2013-2018. Multivariate logistic regression analysis was applied to analyze the association of SES (measured via the ratio of family income to poverty (FIPR), occupation, educational level, and health insurance) and LE8 with clinically relevant depression (CRD) (evaluated using the Patient Health Questionnaire (PHQ-9)). Multiple linear regression analysis was performed to analyze the correlation between SES and LE8. Mediation analysis was carried out to explore the mediating effect of LE8 on the association between SES and CRD. Moreover, these associations were still analyzed by sex, age, and race., Results: A total of 4745 participants with complete PHQ-9 surveys and values to calculated LE8 and SES were included. In the fully adjusted model, individuals with high SES had a significantly higher risk of CRD (odds ratio = 0.21; 95% confidence interval: 0.136 to 0.325, P < 0.01) compared with those with low SES. Moreover, LE8 was estimated to mediate 22.13% of the total association between SES and CRD, and the mediating effect of LE8 varied in different sex and age groups. However, the mediating effect of LE8 in this chain was significant in different sex, age, and racial subgroups except for Mexican American (MA) individuals., Conclusion: The results of our study suggest that LE8 could mediate the association between SES and CRD. Additionally, the mediating effect of LE8 in this chain could be influenced by the race of participants., (© 2024. The Author(s).)