Reduced heart rate variability (HRV) constitutes a widely used marker of cardiac autonomic inflexibility which has been linked to disorders such as panic disorder (PD). To date, the pathophysiological mechanisms whereby panic leads to attenuated HRV are not fully elucidated. We aimed to investigate the hypothesis that PD patients show pathological reactivity both in response to interoceptive and psychosocial stress in comparison to healthy individuals. We performed a controlled study on 38 patients diagnosed with PD [20 males and 18 females aged 35.55 ± 10.12 years, mean ± standard deviation] and 23 age and gender matched healthy control participants. Distress was induced using the Trier Social Stress Test (TSST) and the dexamethasone–corticotropin-releasing-hormone (DEX–CRH) test. We assessed HRV prior to, during, and post-stress induction using the root mean square successive differences (RMSSD) as well as spectral analysis (high frequency; HF and low frequency; LF). Statistical analyses revealed significant main effects of time for mean heart rate (HR), HF, LF (solely DEX–CRH), LFHF-ratio (solely TSST) and the RMSSD. Significant interaction effects were observed with more pronounced increases in mean HR (TSST) and LFHF-ratio (DEX–CRH) in the healthy control participants. No significant main effects of group were observed. Overall, our results indicate ‘‘normal’’ HRV parameters in patients with PD. The HRV of PD patients is no worse than that of healthy control participants since the HRV profiles were similar between the study groups. The current study is one of rather rarely published studies which was unable to show an influence of PD on HRV. Implications for future studies are under discussion.