Background <p>Heart rate variability (HRV) is a cardiac measure that reflects individuals’ ability to adjust their physiological activation at a given time and has been associated with several psychological conditions, including affective disorders like depression and anxiety disorders. The objective of this study was to gain insight into the relationship between HRV and depression and anxiety disorders, and to explore how this association may be reflected in the establishment of the therapeutic alliance (TA) with patients diagnosed with these disorders. We hypothesize that lower levels of symptomatology will be associated with higher HRV, and that the decrease in psychological symptomatology over time will be associated with changes in HRV. Also, drawing on Polyvagal Theory, we hypothesize that higher HRV will be related to stronger TA ratings.</p> Methods <p>The study included 42 participants − 21 individuals with depression or anxiety and 21 healthy controls. HRV was measured during a baseline task and throughout all the psychotherapy sessions. The Outcome Questionnaire and the Working Alliance Inventory were administered at the beginning and at the end of each session respectively for process and outcome and therapeutic alliance assessment. Comparisons of means and mixed generalized linear models were used to test our hypothesis.</p> Results <p>We found that HRV differed between groups at baseline, and we also found evidence for an increase in HRV over the course of therapy. However, the hypothesis that an increase in HRV throughout the therapy would be accompanied by an increase in the TA was not corroborated.</p> Conclusions <p>Our findings support the role of the HRV as an important psychophysiological measure for differentiating emotional disorders from healthy subjects, as well as for tracking changes in clinical symptoms over time.</p>