<p>Recent studies have confirmed a link between obesity and an increased risk of asthma. However, the relationship between serum lipids and asthma remains unclear, and the potential mediating role of immune cells in this association has not been fully elucidated. The present study integrated genome-wide association study (GWAS) data for 179 lipids across 13 lipid species and 731 immune cell phenotypes, representing a broad spectrum of immune cell characteristics, obtained from published literature and public databases. A two-step Mendelian randomization analysis was conducted to investigate the causal effects of the 179 lipids on asthma, with a specific focus on the mediating roles of immune cells. The analysis identified 13 lipids with significant causal associations with asthma, including 10 risk factors and 3 protective factors. The study identified 2 types of immune cells that act as mediators in the causal pathways linking specific lipids to asthma. Particularly, the immune cell phenotype Basophil%CD33^dimHLA-DR⁻CD66b⁻ exhibited a substantial mediating effect in the association between triacylglycerol (50:2) levels and asthma (Mediated effect = 0.00794; Mediated proportion = 10.5%). Triacylglycerol (50:2) was identified as a risk factor for asthma development. The immune cell phenotype Basophil%CD33^dimHLA-DR⁻CD66b⁻ significantly mediates the causal relationship between triacylglycerol (50:2) levels and asthma. The combination of triglyceride levels and basophil counts may serve as potential auxiliary indicators for the clinical screening of asthma. Targeting triacylglycerols and basophil cells may provide new directions for the treatment of asthma.</p>