Systemic perturbations such as peripheral surgical trauma induce neurovascular, inflammatory, and cognitive changes. The blood-brain barrier is a key interface between the periphery and the central nervous system, and is critically involved in regulating neuroimmune interactions to maintain overall homeostasis. Mounting evidence suggests that blood-brain barrier dysfunction is a hallmark of ageing and multiple neurological conditions including Alzheimer's disease. We discuss a recent study published in the British Journal of Anaesthesia that describes blood-brain barrier changes and neuroinflammation in patients with postoperative delirium after non-intracranial surgery.