This study investigated the psychophysiological correlates of the subjective experience of vicarious pain; that is, a spontaneous experience of pain when seeing another in pain. Forty-nine healthy, otherwise pain-free individuals aged 18-55 years completed empathy and anxiety questionnaires and were classified into three groups: vicarious responders with high anxiety (n=11), vicarious responders with low anxiety (n=22), and nonresponders (n=16). Electrophysiological recordings of heart rate variability (HRV) during paced breathing and cognitive stress (serial sevens task) were completed before participants viewed short videos of athletes in states of pain or happiness, taken from Australian League Football matches. Change in beats per minute, relative to neutral scenes, were analyzed for the first 4 s after onset of the painful or happy event. Anxious responders had lower HF-HRV than both other groups, implicating poor parasympathetic regulation specific to states of stress. Both vicarious responder groups had elevated HR at the event onset, regardless of valence. After viewing painful injuries, nonanxious vicarious responders showed sustained HR over time, anxious responders showed HR acceleration with a peak at 3 s after the injury onset, and nonresponders showed a pattern of marked HR deceleration. These findings suggest that vicarious pain in anxious responders is associated with poorly regulated sympathetic arousal via insufficient inhibitory parasympathetic activity, whereas nonanxious persons show sustained arousal. Clearly, multiple mechanisms in the central and peripheral nervous system must play a role in vicarious pain states, and the different manifestations are likely to lead to very different behavioral consequences.