The aim of this study was to examine the association between sympathetic nervous activity, depressive symptoms, and metabolic syndrome in a sample of black and Caucasian Africans. The sample consisted of healthy men and women: 194 blacks (aged, mean ± SD, 44.1 ± 7.9 years) and 206 Caucasians (aged, mean ± SD, 44.7 ± 10.8 years). Salivary 3-methoxy-phenylglycol (MHPG) concentration, the major metabolite of norepinephrine, was measured during the Stroop mental challenge. Depressive symptoms were assessed from the 9-item Patient Health Questionnaire. Metabolic syndrome (defined as central obesity plus any other two risk factors including raised serum triglycerides, reduced serum high-density lipoprotein- cholesterol, raised blood pressure, and raised fasting plasma glucose) was prevalent in 43.0% and 36.4% of blacks and Caucasians, respectively. In blacks there was, on average, a 16.4% increase in salivary MHPG concentration following mental stress, although no significant response was observed in Caucasians. The salivary MHPG response in blacks was associated with risk of metabolic syndrome (odds ratio [OR] = 1.11, 95% CI, 1.00-1.24) after adjusting for age, sex, and baseline salivary MHPG concentration. This association was mainly driven by the central obesity component of the metabolic syndrome. The salivary MHPG response was also related to moderate-severe depressive symptoms (OR = 1.16, 95% CI, 1.04-1.30), and further adjustment for depressive symptoms attenuated the association between salivary MHPG response and metabolic syndrome (OR = 1.07, 95% CI, 0.96-1.20). These data indicate an association between sympathetic activity, depressive symptoms, and metabolic syndrome in a sample of black Africans.