Meditators’ brains responded to the coupling of death and self-stimuli in a manner indicating acceptance rather than denial, corresponding to increased self-reported well-being. Additionally, degree of death acceptance predicted positively valenced meditation-induced self-dissolution experiences, thus shedding light on possible mechanisms underlying wholesome vs pathological disruptions to self-consciousness. The findings provide empirical support for the hypothesis that the neural mechanisms underlying the human tendency to avoid death are not hard-wired but are amenable to mental training, one which is linked with meditating on the experience of the embodied self’s impermanence. The results also highlight the importance of assessing and addressing mortality concerns when implementing psychopharmacological or contemplative interventions with the potential of inducing radical disruptions to self-consciousness.