Social pain is a painful experience caused by negative events, such as relationship broken, undervaluation, and social rejection. In this review, we summarized the neurophysiological mechanisms of social pain from perspectives of neuroimaging, neuroendocrine and neuroimmunology. Future studies are warranted to further determine the relationship between physical and social pain, explore the characteristics and neural mechanism of social pain in mental disorders (such as schizophrenia and autism), and investigate the mechanism of memory for social pain.