The objective of this study was to examine the role of obesity in the development of the metabolic syndrome (MS). A total of 3,596 whites aged 19 years and above, who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2002, were included for analysis. Anthropometric measurements, biochemical profiles, and high-sensitivity C-reactive protein (CRP) were measured. A structural equation model (SEM) was constructed to elucidate a pathway in which obesity initiated the cascade leading to full MS. The results of SEM demonstrated that obesity was positively associated with elevated CRP level (B = 0.05, P < 0.001). This higher inflammatory state directed to insulin resistance (B = 0.32, P < 0.001), which in turn was positively associated with dyslipidemia (B = 0.06, P < 0.001). Obesity could also directly and positively affect blood pressure (B = 0.51, P < 0.001), without the mediation of insulin resistance and/or inflammation. The results of the cross-sectional analysis in the white subjects have shown that obesity has a strong influence on hypertension that obtains little additional influence from inflammation or insulin resistance. The metabolic profile in the NHANES group has been confirmatory with the statement that there is a sequential effect from obesity to inflammation, insulin resistance, and dyslipidemia. This approach has allowed to inferring important biological insights about the nature of the relationships among the components of MS.