Background: Since panic is characterized by stress-induced autonomic cardiac sensations, such as increased heart rate and palpitations, effects of experimental psycho-social stress on heart rate variability are of interest. Methods: 25 patients with a current panic disorder and 25 healthy controls matched by age and sex underwent the Trier Social Stress Test on two consecutive days. Heart rate and heart rate variability (HRV) were assessed before and during test performance as well as under recovery conditions. Results: An increase of heart rate was observed in both patients suffering from panic disorder and in healthy controls under conditions of experimental psycho-social stress. Root mean square successive differences (RMSSD), a time domain parameter of HRV, was decreased in both groups of participants during the stress conditions. Low frequency/high frequency ratio (LF/HF), a frequency domain parameter of HRV, was found increased in patients with panic disorder when performing the Trier Social Stress Test whereas no such change was found in healthy controls. Conclusions: Induction of psychosocial stress increases heart rate and impairs heart rate variability. The latter effect reflects activation of the sympathetic and/or inhibition of the parasympathetic autonomous nervous system (ANS) that is more pronounced in patients suffering from panic disorder than in healthy controls.