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Aim To screen the early and advanced atherosclerosis differential genes associated with cuproptosis by bioinformatic methods, and analyze their mechanisms of action, and predict potential biomarkers. Methods The information related to early and advanced atherosclerosis (GSE28829 and GSE43292 data sets) was downloaded from GEO database and standardized. 19 cuproptosis genes were obtained from the literature. Difference analysis, enrichment analysis, consensus clustering algorithm, principal component analysis, immune cell infiltration and screening core genes were used to find their action mechanisms and potential biomarkers. Results Finally, 10 differential genes related to cuproptosis were screened. The correlation analysis of differential genes related to cuproptosis showed a strong positive correlation between GLS and DBT (r =0. 78, P<0. 001), while NLRP3 showed a strong negative correlation with DBT and GLS (r =-0. 62, P<0. 001). GO enrichment analysis of differential genes related to cuproptosis was mainly related to copper ion transport and copper homeostasis, and KEGG analysis showed that it was mainly enriched in platinum resistance, mineral absorption and central carbon metabolic pathway in cancer. The PPI network analysis and MCODE were used to screen core genes. The results of immune cell infiltration showed that M2 macrophages, M0 macrophages, resting CD4 memory T cells, and CD8+ T cells were dominant (P<0. 05). The correlation analysis of differential genes related to immune cells and cuproptosis showed that in the early stage of atherosclerosis, GLS was strongly positively correlated with activated NK cells (r =0. 52, P<0. 001), FDX1 and SLC31A1 was strongestly negatively correlated with CD8+ T cells (r = -0. 51, P<0. 001); in the advanced stage of atherosclerosis, FDX1 was strongestly positively correlated with M0 macrophages (r =0. 58, P<0. 001) and FDX1 was strongestly negatively correlated with CD8+ T cells (r =-0. 55, P<0. 001). Principal component analysis showed that two subtypes C1 and C2 could be clearly distinguished according to the expression of cuproptosis-related differential genes. Conclusion The immune-related changes between cuproptosis and the development of atherosclerosis may be the key to the diagnosis and treatment of early and advanced atherosclerosis, and the core genes SLC31A1, MTF1, ATP7B and ATP7A may be potential markers and therapeutic targets for the development of atherosclerosis. [ABSTRACT FROM AUTHOR]