Empathy for another’s physical pain has been demonstrated in humans 1 and mice 2; in both species, empathy is stronger between familiars. Stress levels in stranger dyads are higher than in cagemate dyads or isolated mice 2, 3, suggesting that stress might be responsible for the absence of empathy for the pain of strangers. We show here that blockade of glucocorticoid synthesis or receptors for adrenal stress hormones elicits the expression of emotional contagion (a form of empathy) in strangers of both species. Mice and undergraduates were tested for sensitivity to noxious stimulation alone and/or together (dyads). In familiar, but not stranger, pairs, dyadic testing was associated with increased pain behaviors or ratings compared to isolated testing. Pharmacological blockade of glucocorticoid synthesis or glucocorticoid and mineralocorticoid receptors enabled the expression of emotional contagion of pain in mouse and human stranger dyads, as did a shared gaming experience (the video game Rock Band) in human strangers. Our results demonstrate that emotional contagion is prevented, in an evolutionarily conserved manner, by the stress of a social interaction with an unfamiliar conspecific and can be evoked by blocking the endocrine stress response. •Emotional contagion of pain in stranger mice can be elicited by stress reduction•Emotional contagion of pain in cagemate mice can be blocked by stress•Emotional contagion of pain in humans occurs in friends, but not strangers•Stress reduction in humans can elicit emotional contagion of pain in strangers Emotional contagion of pain can be observed, in both mice and humans, among familiar, but not stranger, dyads. Martin et al. show here that pharmacological or psychological stress reduction can elicit the phenomenon in stranger dyads. This suggests that stress is the key to emotional contagion, the fundamental building block of empathy.