Lonely people evaluate social exchanges and relationships negatively and display difficulties in interpersonal interaction. Interpersonal synchronization is crucial for achieving positive interactions, promoting affinity, closeness, and satisfaction. However, little is known about lonely individuals ability to synchronize and about the activity in the lonely brain while synchronizing. In the present neuroimaging study, 64 participants engaged in interpersonal synchronization, using a novel paradigm involving real dyadic interaction. Results show that high loneliness individuals exhibited a reduced ability to adapt their movement to their partners movement. Intriguingly, during periods in which participants adapted their movement, high loneliness individuals showed increased activation in the observation-execution (OE) system, specifically in the inferior frontal gyrus (IFG) and the inferior parietal lobule (IPL). They did not show increased activation in the dmPFC, which in the context of synchronization was suggested to be related to gap-monitoring. Based on these findings, we propose a model according to which lonely people may require a stronger activation of their OE system for movement alignment to compensate for some deficiency in their ability to synchronize. However, despite this hyper-activation, they still suffer from reduced synchronization capacity. Consequently, synchronization may be a relevant intervention area for the amelioration of chronic loneliness.