Background <p>Empathy for pain refers to a simulation of pain experiences evoked when seeing others in pain. Empathy for pain (vicarious pain) responders make up 27% of the healthy population, and are divided into two subsets: Sensory/Localized responders who feel localized physical pain and Affective/General responders who experience diffuse emotional pain. Empathy for pain is linked to pro-social behavior but can increase mental health symptoms.</p> Methods <p>Multivariate analysis of variance and latent variable mediation model were used to investigate the relationship between empathy for pain, mental health, and emotion regulation based on a university student dataset (mainly Caucasian) from 2020 to 2021.</p> Results <p>(1) Responders express significantly higher anxiety and somatization than non-responders, with Sensory/Localized responders reporting the greatest somatic concerns; (2) Sensory/localized responders show significantly higher depression than non-responders; (3) Two responder groups don’t differ from non-responders on most positive emotional regulation strategies, but use more negative strategies (self-blame, rumination, and catastrophizing). (4) negative emotional regulation fully mediates the link between empathy and mental health.</p> Conclusions <p>These findings reveal a previously unrecognized link between empathy for pain and mental health, mediated by the increased use of negative emotion regulation strategies among responders. Our findings have particular implications for the mental health of empathic individuals or people who are often exposed to the pain of others (counselor or nurse, etc.).</p>