Negative pressure wound therapy (NPWT) has been adopted as the first-line treatment for poststernotomy mediastinitis as a result of the excellent clinical outcome. The knowledge concerning the effects of NPWT on the cardiovascular system and homeostasis is still limited. The aim of the present study was to investigate whether the plasma levels of neurohormones change during NPWT. Six pigs underwent median sternotomy followed by NPWT at -125 mmHg. The plasma levels of noradrenaline, adrenaline, neuropeptide Y, substance P, vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) were determined before (0 min) and 5, 20, 60 and 180 min after the application of NPWT. The results show a transient increase in the plasma levels of noradrenaline and adrenaline when NPWT was applied. The plasma level of the adrenergic co-transmitter neuropeptide Y was higher in NPWT - than in sham-treated pigs, after 180 min of negative pressure. After 180 min of NPWT there was an increase in the plasma levels of the sensory nerve transmitter substance P, while no such effect was observed for CGRP or VIP. In conclusion, the results suggest sympathetic nerve activation during NPWT. This may be the result of an increase in workload on the heart during the initial phase of NPWT. Keywords: Experimental surgery; Mediastinal infection; Wound healing; Noradrenaline; Adrenaline.