Objective: Recent evidence indicates that stress is associated with obesity, hypertension and metabolic abnormalities. Stress pathways, including both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, are activated in individuals with the metabolic syndrome. In order to gain some insight into the relation between sympathetic nervous system activation, metabolic profile and stress, we examined the pattern of sympathetic nervous firing in eight women and 17 men with the metabolic syndrome and elevated blood pressure (BP) in relation to their underlying psychological stress. Methods and Results: Both multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded by using the technique of microneurography and psychological stress was assessed by Spielberger's State and Trait Anxiety scores and the Beck Depression Inventory II (BDI-II). Women had higher cholesterol levels, higher depressive symptom scores and similar multiunit MSNA compared with the men but displayed a disturbed firing pattern of sympathetic activity as indicated by a higher incidence of multiple spikes per burst (P < 0.05). In all individuals, regression analysis after adjustment for sex indicated that the single-unit sympathetic nerve-firing pattern did not correlate with any aspect of the metabolic profile; however it was significantly associated with anxiety state and trait and the affective component of the BDI scores. In particular, higher incidence of multiple firing (more than two spikes) during a sympathetic neural burst was associated with higher trait anxiety score (R = 0.557, P = 0.004) and higher affective depressive symptoms (R = 0.517, P = 0.008). Somatic symptoms bore no association with the sympathetic firing pattern. Conclusion: These results suggest that chronic mental stress modulates the pattern of sympathetic activity, which, in turn, may confer greater cardiovascular risk on individuals with the metabolic syndrome and elevated BP.