Humans are constantly exposed to liquid crystal monomers (LCMs) due to the widespread use of various electronic products. Previous studies have shown that LCMs can cause dysregulation in gene expression related to lipid homeostasis. However, the quantitative associations and effects of exposure to individual and mixed LCMs on blood lipid levels remain poorly understood. This study measured the serum concentrations of 57 LCMs, along with total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), in 78 adults in South China. Among the participants, 51 LCMs were detected in serum samples, with detection frequencies ranging from 1.30% to 75.6% and concentrations from 2.58 to 86.29 ng/mL. Results from generalized linear and restricted cubic splines models demonstrated distinct effects of individual LCMs on lipid levels, with non-monotonic dose-response relationship curves. The application of generalized weighted quantile sum (gWQS) analysis revealed that the constructed weighted quantile sum (WQS) index was negatively correlated with HDL-C levels (Coefficient: −0.44, 95% CI: −0.64 to −0.25, P = 0.030), with 4-(4-Ethylcyclohexyl) benzonitrile (EtCBN), 4-Methyl-4'-pentylbiphenyl (MPB) and 2'-Fluoro-4-Pentyl-4''-Propyl-1,1':4',1''-Terphenyl (PFPT) contributing most significantly to this association. Our findings highlight the overall dose-dependent effects of LCM exposure and provide further evidence of dyslipidemia associated with LCM mixtures.