Out-of-body experiences (OBEs) are subjective phenomena during which individuals feel disembodied or perceive themselves as outside of their physical bodies, often resulting in profound and transformative effects. In particular, experiencers report greater heightened pro-social behavior, including more peaceful relationships, tolerance, and empathy. Drawing parallels with the phenomenon of ego dissolution induced by certain psychedelic substances, we explore the notion that OBEs may engender these changes through ego dissolution, which fosters a deep-seated sense of unity and interconnectedness with others. We then assess potential brain mechanisms underlying the link between OBEs and empathy, considering the involvement of the temporoparietal junction and the Default Mode Network. This manuscript offers an examination of the potential pathways through which OBEs catalyze empathic enhancement, shedding light on the intricate interplay between altered states of consciousness and human empathy. •Out-of-body experiences (OBEs) have a profound impact on individuals’ lives.•A persisting effect of OBEs is heightened prosocial behavior such as empathy.•We propose that OBEs may engender these changes through ego dissolution.•Ego dissolution fosters a sense of unity and interconnectedness with others.•The temporoparietal junction and the Default Mode Network may mediate this process.