Katarzyna Jakuszkowiak-Wojten, Jerzy Landowski, Mariusz S Wiglusz, Wiesław Jerzy Cubała Department of Psychiatry, Medical University of Gdansk, Gdansk, Poland Background: It is unclear whether hypothalamic–pituitary–adrenal axis is involved in the pathophysiology of panic disorder (PD). The findings remain inconsistent. Cortisol awakening response (CAR) is a noninvasive biomarker of stress system activity. We designed the study to assess CAR in drug-naïve PD patients.   Materials and methods: We assessed CAR in 14 psychotropic drug-naïve outpatients with PD and 14 healthy controls. The severity of PD was assessed with Panic and Agoraphobia Scale. The severity of anxiety and depression was screened with Hospital Anxiety and Depression Scale.   Results: No significant difference in CAR between PD patients and control group was found. No correlations were observed between CAR and anxiety severity measures in PD patients and controls.   Limitations: The number of participating subjects was relatively small, and the study results apply to nonsuicidal drug-naïve PD patients without agoraphobia and with short-illness duration. There was a lack of control on subjects’ compliance with the sampling instructions.  Conclusion: The study provides no support for elevated CAR levels in drug-naïve PD patients without agoraphobia. Keywords: panic disorder, PD, CAR, cortisol awakening response, HPA axis, hypothalamic–pituitary–adrenal axis