Obesity and metabolic syndrome (MS), which often co-exist, are associated with an increased cardiovascular risk. An increased leukocyte count is also associated with an increased cardiovascular risk. However, the role of obesity, independent of MS, has been debated. We sought to assess the influence of MS on the association of obesity and leukocyte count in asymptomatic patients. The data from 431 asymptomatic Brazilian men (mean age 46 +/- 7 years), who presented for cardiovascular risk assessment, were analyzed. MS was defined as the presence of > or =3 of the following risk factors: hypertension (> or =130/85 mm Hg), truncal obesity (> or =102 cm or 40 in), hypertriglyceridemia (> or =150 mg/dl), high-density lipoprotein cholesterol (< or =40 mg/dl), and hyperglycemia (glucose > or =110 mg/dl). Obesity was defined as a body mass index of > or =30 kg/m(2). Confounding variables (age, smoking, lipid-lowering therapy, and physical activity) and leukocyte count (10(9)/L) were recorded. The patients were divided into 4 groups: group1, no obesity and no MS; group 2, obesity but no MS; group 3, no obesity but MS; and group 4, obesity and MS. The mean leukocyte count increased from groups 1 to 4 (6.10 +/- 0.09, 6.42 +/- 0.28, 6.71 +/- 0.21, and 6.96 +/- 0.22 x 10(9)/L, p < 0.001 for trend). Multivariate regression analysis demonstrated that the leukocyte count was significantly higher in groups 3 (coefficient 0.61, p = 0.007) and 4 (coefficient 0.86, p < 0.001) compared with group 1. However, no significant difference was found in the leukocyte count between groups 1 and 2 (coefficient 0.29, p = 0.42) and groups 3 and 4 (coefficient 0.25, p = 0.41). The association between obesity and leukocyte count was highly dependent on the presence of MS.