Adipocyte death caused by local inflammation is one feature in the early biological development of metabolic unhealthy and diabetes. When cells become necrotic or apoptotic, cell DNA is released into the bloodstream, which is known as cell-free DNA (cfDNA). DNA methylation is cell type-specific and each cell type has its unique DNA methylation pattern. Detecting cell-type-specific DNA methylation levels reflect the presence of certain cell in samples. Therefore, by identifying adipocyte/liver-specific DNA methylation in plasma, we could infer the adipocyte/liver death and metabolic unhealthy. Here, we propose a novel approach to determine the metabolic health status by detecting adipocyte and liver-specific DNA methylation markers from plasma and validate the analytic utility of this assay. We firstly identified the differential methylation at CpG loci specific to adipocyte and liver using 323 whole-genome bisulfite sequencing samples consisted of 28 types of tissues. We then designed the methylation-specific PCR assay to detect liver and adipose signals. A Four-plex assay with two adipose- and one liver-specific methylation locus was designed to detect cfDNA elevated in response to metabolic health. We also verified the analytical utility of this metabolic assay in 42 cfDNA samples extracted from lean and obese patients' plasma using digital droplet PCR. Our assay results demonstrated Metabolic Abnormal Obese (MAO) people have a higher adipose and liver cfDNA concentration (median: 2.5 and 10 copies/mL plasma, respectively) compared to that in Metabolic Healthy Obese (MHO) (median: 1.5 and 3.5 copies/mL plasma, respectively) and lean groups (median: 1.4 and 4 copies/mL plasma, respectively). MAO patients usually have a significantly higher percentage of adipose and liver in cfDNA (1.8%) than MHO and lean patients (0.7% and 1.1%). In summary, our proof-of-concept study shows that our novel metabolic assay distinguishes MAO from MHO and lean. This promising assay enables precise stratification for metabolic unhealthy and diabetes.