The association between psoriasis and cardiovascular diseases has been indicated by epidemiological studies. The sub-inflammatory systemic state that characterizes both psoriasis and atherosclerosis has been proposed as the link between these conditions; it cannot, however, explain the increased incidence of sudden cardiac death reported in young patients with severe psoriasis without common cardiovascular risk factors. In a previous study, we reported higher levels of autonomic dysregulation in patients with psoriasis, concluding that the prevalence of the sympathetic arm over the parasympathetic could increase cardiovascular risk. Objective of this study was to assess the influence of etanercept on autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. Five-minute ECG recordings were collected at rest before and after 12 weeks of therapy with etanercept in 19 young patients with psoriasis without cardiovascular risk factors. The Cardiolab CE pocket PC ECG system was used for linear methods of heart rate variability (HRV) analysis. No significant change in HRV analysis parameters was apparent after 12 weeks of etanercept therapy. Our data suggest that treatment with etanercept in patients with moderate-to-severe psoriasis does not affect cardiovascular autonomic regulation and cardiovascular risk.