In line with the growing recognition of the role of embodiment, affect and implicit processes in psychotherapy, several recent studies examine the role of physiological synchrony in the process and outcome of psychotherapy. This study aims to introduce Partial Directed Coherence (PDC) as a novel approach to calculating psychophysiological synchrony and examine its potential to contribute to our understanding of the therapy process. The study adopts a single-case, mixed-method design and examines physiological synchrony in one-couple therapy in relation to the therapeutic alliance and a narrative analysis of meaning construction in the sessions. Interpersonal Physiological Synchrony (IPS) was calculated, via a windowed approach, through PDC of a Heart Rate Variability-derived physiological index, which was measured in the third and penultimate sessions. Our mixed-method analysis shows that PDC quantified significant moments of IPS within and across the sessions, modeling the characteristics of interpersonal interaction as well as the effects of therapy on the interactional dynamics. The findings of this study point to the complex interplay between explicit and implicit levels of interaction and the potential contribution of including physiological synchrony in the study of interactional processes in psychotherapy.