Non-neurological complications are common after brain injury and their importance as independent contributors to morbidity and mortality are well recognized. This chapter reviews the aetiology of systemic complications in critically ill neurological patients, identifies options for their prevention and treatment, and considers their effects on outcome. Several central nervous system (CNS)-driven changes contribute to systemic organ dysfunction after brain injury. These include catecholamine- and inflammatory- related effects, as well as endocrine and coagulation abnormalities. The chapter outlines the sequelae of brain injury that are related to endogenous catecholamine release, activation of adrenoceptors and neuroinflammation. It also considers the neuroendocrine and electrolyte disturbance, and other causes of non-neurological organ dysfunction. The complex interaction between the brain and immune system, including the systemic effects of neuroinflammation, is mediated through neuroendocrine pathways including the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Haematological complications, particularly coagulopathy, occur in 20-36% of patients after brain injury.