Perinatal mortality is increased considerably in multiple pregnancies compared to singleton pregnancies, with single intrauterine fetal demise (sIUFD) presenting a rare but unique perinatal problem. Monochorionic pregnancies are at particular risk of sIUFD due to bidirectional inter-twin placental vascular anastomoses. The resulting inter-twin blood flow can become unbalanced, causing acute and chronic inter-twin transfusion and profound anemia secondary to fetal exsanguination into the low-pressure circulation of the dead fetus. If the sIUFD occurs after 14 weeks’ gestation it is believed to have the most significant effect on the continuing pregnancy as the co-twin is at increased risk of preterm delivery, long-term neurological complications, and death. This article will focus on fetal brain injury in the surviving co-twin in the case of sIUFD, as it is the most common kind of injury in sIUFD, and one which concerns parents and may be the basis for terminating the pregnancy. We will outline how these brain injuries are thought to occur and describe potential pathophysiological mechanisms. We will discuss risk factors for brain injury in cases of sIUFD, including: chorionicity, cause of the sIUFD (spontaneous or secondary to an underlying pathological process such as twin-to-twin transfusion syndrome), gestation of delivery and how to prevent brain injury in the co-twin. We also review modes of imaging, discuss the difficulties in predicting the long-term outcome for co-twin survivors, and highlight the dearth of research in this area.