The pathogenesis of depression is related to immune inflammatory response. Atherogenic coefficient (AC) is an important indicator of lipid abnormalities, which can lead to immune inflammatory responses. However, no study has investigated the relationship between AC and depression in adult Americans. Therefore, we investigated this relationship.This study used a cross-sectional design.The National Health and Nutrition Examination Survey (2005-2018) data were used for this study.A total of 32 502 participants aged 20 years or older who had complete information for AC and depression were included in this study.Depressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9), with a cut-off point of 9/10 indicating likely depression cases. Weighted logistic regression analyses and the smooth curve fittings were performed to explore the association between AC and depression.After adjusting for potential confounders, a single unit increase in AC was associated with a 3% increase in the prevalence of depression (HR=1.03, 95% CI=1.00 to 1.06, p=0.039). The relationship between AC and depression was more obvious in females.The AC is positively associated with depression.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.