Obestatin, derived from the same gene as the hunger hormone ghrelin, may reduce food intake in animals. The role of obestatin in human physiology is unclear. We evaluated cross-sectional associations between participant characteristics and fasting levels of obestatin as well two other hormones associated with energy balance, ghrelin and leptin. Data are from the baseline visit of the Optimal Macronutrient Intake Trial to Prevent Heart Disease (OMNI-Heart) Trial that enrolled adults with elevated blood pressure (systolic 120-159 mm Hg or a diastolic of 80-99 mm Hg) but who were otherwise healthy. Partial Spearman's correlations and linear regression models estimated the association between age, gender, BMI, physical activity, and smoking with fasting hormones. Obestatin was directly associated with ghrelin (r = 0.45, P < 0.05). On average, overweight (BMI 25-30) and obese (BMI > 30) individuals had obestatin concentrations that were 12.6 (s.d. 8.8) and 25.4 (s.d. 8.4) pg/ml lower compared to normal weight (BMI < 25) individuals, respectively (P for trend = 0.002). Overweight (BMI 25-30) and obese (BMI > 30) individuals had ghrelin concentrations that were 161.7 (s.d. 69.6) and 284.7 (s.d. 66.5) pg/ml lower compared to normal weight (BMI < 25) individuals, respectively (P for trend <0.0001). A 5 unit increase in BMI was associated with 41.3% (s.d. 4.3%) (P < 0.0001) higher leptin. Obestatin and ghrelin are directly correlated and share the same patterns of association with participant characteristics. Modifiable risk factors for chronic diseases, such as BMI, are associated with fasting levels of leptin, obestatin, and ghrelin.