Chemerin is an adipokine that may mediate the link between obesity, inflammation, insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. In this study, we examined the association between chemerin and various cardiometabolic risk factors in cross-sectional setting and tested the hypothesis that a 6-month combined exercise program decreases serum chemerin in overweight or obese, non-diabetic individuals. Serum chemerin concentration was measured in a cross-sectional analysis including 98 individuals with a wide range of age and body mass index (BMI). In addition, chemerin was measured in 79 sedentary, overweight or obese, non-diabetic individuals who completed a 6-month combined endurance and resistance exercise program (CEP, n = 51) or served as controls (C, n = 28). Chemerin was significantly associated with total cholesterol (p = 0.04), triglycerides (p < 0.001), fasting insulin (p < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR, p < 0.001), systolic blood pressure (p = 0.04), highly sensitive C-reactive protein (p = 0.03), leucocytes count (p = 0.047), and leptin (p = 0.008) independently of age and BMI. In multiple regression analysis, chemerin was an independent determinant of HOMA-IR. As a result of the 6-month training program, serum chemerin decreased significantly in CEP group (-13.8 ± 13.2 ng/ml, p < 0.001). A significant association between the changes in chemerin and improved HOMA-IR were found even after adjustment for changes in waist circumference. Among non-diabetic individuals serum chemerin was associated with various cardiometabolic risk factors independently of BMI. In addition, the 6-month combined strength and endurance training program led to a significant reduction in circulating chemerin levels in overweight or obese individuals.