Various leukocyte-to-high-density lipoprotein cholesterol (HDL-C) ratios, namely the neutrophil to HDL-C ratio (NHR), lymphocyte to HDL-C ratio (LHR), and monocyte to HDL-C ratio (MHR), have been identified as potential inflammatory biomarkers. Despite this, the intricate relationship between these ratios and Cardiovascular-Kidney-Metabolic (CKM) Syndrome has yet to be fully elucidated. This study aims to explore the associations between these white blood cell ratios and the presence of CKM Syndrome. This cross-sectional retrospective analysis utilized data from 19,534 individuals diagnosed with CKM Syndrome, sourced from the National Health and Nutrition Examination Survey (NHANES) database covering the years 1999-2020. Participants were stratified, and relevant covariates were adjusted during the analysis. Weighted logistic regression models were employed to statistically assess the relationships between the inflammatory markers and the differing stages of CKM Syndrome, with stage 0 serving as the reference point. After adjusting for all the covariates, high levels of three inflammatory indicators were associated with higher odds of having CKM Syndrome stage 1-4, using stage 0 as a reference. When we assessed the associations between inflammatory indicators with stage 3-4 with stage 0-1-2 as the reference group, we found that inflammatory indicators still increased the risk of higher CKM Syndrome stage. The dose-response relationship revealed that the inflammatory indicators increased the risk of higher CKM Syndrome stage. After conducting subgroup analyses, we found that LHR and education, as well as LHR, MHR, and drinking status, had significant interactions. Elevated NHR, LHR, and MHR are significantly associated with an increased risk of CKM Syndrome across stages 1-4.