We investigated emotional processing in vicarious pain (VP) responders. VP responders report an explicit sensory and emotional feeling of pain when they witness another in pain, which is greater in magnitude than the empathic processing of pain in the general population. In Study 1, 31 participants completed a chimeric faces task, judging whether emotional chimera in the left, or right, visual field was more intense. VP responders took longer to judge emotionality than non-responders, and fixated more on the angry hemiface in the right visual field, whereas non-responder controls had no lateralized fixation bias. In Study 2, blood-oxygen level-dependent signals were recorded during an emotional face matching task. VP intensity was correlated with increased insula activity and reduced middle frontal gyrus activity for angry faces, and with reduced activity in the inferior and middle frontal gyri for sad faces. Together, these findings suggest that VP responders are more reactive to negative emotional expressions. Specifically, emotional judgements involved altered left-hemisphere activity in VP responders, and reduced engagement of regions involved in emotion regulation.