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The practice of bondage/discipline, dominance/submission, sadism/masochism (BDSM) sometimes is associated with giving and receiving pain. It remains unresolved how BDSM practitioners perceive the pain of other people. This study investigated whether and how the BDSM experience affects human empathy. Experiment 1 measured trait empathy and subjective empathic responses in BDSM practitioners and control respondents. The results revealed lower trait empathy scores and subjective pain intensity ratings in the female submissive group (Subs) compared to controls. Experiment 2 measured participants’ neural responses to others’ suffering by recording event-related potentials (ERPs) from female Subs and controls while viewing painful and neutral expressions. We found that the differential amplitudes between painful and neutral expressions in the frontal N1 (92–112 ms), frontal P2 (132–172 ms) and central late LPP (700–1000 ms) were reduced in the submissive group versus the control group. These findings suggest that being in the submissive role during BDSM practice weakens female individuals’ empathic responses to others’ suffering at both the behavioral and neural levels.Involving in BDSM relationships and practices did not necessarily result in weaken empathy abilities.Female submissives’ empathic responses were weakened at both behavioral/psychological and neural levels.Both early automatic empathic responses and late controlled processes were modulated by BDSM experiences in the female subs.