Introduction: Plasma and serum water T 2 are global markers of metabolic syndrome and cardiometabolic health. Serum, in contrast with plasma, lacks fibrinogen, one of the key drivers of the association of plasma water T 2 with metabolic syndrome. Yet, serum water T 2 was able to detect metabolic syndrome with high sensitivity and specificity through its association with other underlying components. Here we examined bio-banked serum samples from a large, diverse study population to investigate the use of serum water T 2 as a marker of cardiometabolic health. Hypothesis: Among PREMIER participants at baseline, serum water T 2 is associated with multiple measures of cardiometabolic health. Materials and Methods: This is an auxiliary study of the PREMIER trial and has an observational, cross-sectional design. A total of 810 mildly hypertensive participants without diabetes or CVD (63% females, 35% black, and 65% non-black) were enrolled in the parent study. Here, a subset of those participants (n=455) were analyzed based on the availability of serum samples that had undergone a single freeze-thaw cycle. Using a Bruker mq20 benchtop nuclear magnetic resonance relaxometer, T 2 decay curves were recorded at 37°C for unmodified human serum. Water T 2 was distinguished from non-water components using a discrete inverse Laplace transform algorithm. The association of serum water T 2 , the outcome variable, with other potential predictors was examined in four stages: (1) screening of predictors using a bootstrap forest machine learning algorithm, (2) clustering of predictors using principal component analysis, (3) associations with serum water T 2 using multiple linear regression, and (4) validation of regression models using a bootstrap forest algorithm. Results: The final model for serum water T 2 included albumin, globulins, non-HDL-cholesterol, household income, urine phosphate, TG/HDL ratio, family history of CVD and the interaction between BMI and race. The adjusted R 2 for this model was 0.55. Thus, serum water T 2 values were independently associated with markers of dyslipidemia, inflammation, insulin resistance, kidney function, family history of CVD, household income, and the categorical interaction between BMI and race. Compared with obese/Black individuals (reference group), non-obese/non-Black individuals showed higher T 2 values (p<0.0001) reflecting improved cardiometabolic health. By contrast, serum water T 2 values for the non-obese/Black (p=0.7417) and obese/non-Black (p=0.7262) participants were not statistically different from the reference group. Conclusion: Analysis of bio-banked samples from PREMIER validates serum water T 2 as a biomarker of cardiometabolic health in mildly hypertensive individuals without diabetes or CVD. Serum water T 2 , while similar to plasma water T 2 , revealed some distinct associations with measures of cardiometabolic health.