Objective. There is a growing consensus that interpersonal processes are key to understanding psychotherapy. How might that be reflected in the brain? Recent research proposes that inter-brain synchrony is a crucial neural component of interpersonal interaction. The current proof-of-concept study examines, for the first time, therapist-patient inter-brain synchrony measurement during multiple sessions. To guide the design of future studies, we performed a precursory test in a small sample of the association between inter-brain synchrony and therapeutic change, hypothesizing that it would gradually increase over therapy, reflecting inter-brain plasticity. Method. We scanned 18 therapy sessions of participants (N = 8) who underwent a 6-session test anxiety treatment. We measured therapist and patient brain activity using functional near-infrared spectroscopy (fNIRS) and assessed perceived session quality, wellbeing, symptoms, and therapeutic alliance every session. Results. In this proof-of-concept sample inter-brain synchrony gradually increased over treatment, and was associated with reduced symptoms, improved wellbeing and perceived session quality, but not with a stronger therapeutic alliance. fNIRS imaging had no discernable adverse effects. Conclusion. Our findings demonstrate that fNIRS imaging during psychotherapy is a feasible and viable research method and that inter-brain plasticity should be a candidate for future research on biological mechanisms underlying therapeutic change.