The aim of this study was to investigate the impact of noise exposure in an intensive care unit (ICU) environment on the development of postoperative delirium in a mouse model that mimics the ICU environment. Additionally, we aimed to identify the underlying mechanisms contributing to delirium and provide evidence for reducing the risk of delirium. In this study, to mimic an ICU environment, lipopolysaccharide (LPS)-injected sepsis mouse models were exposed to a 75 dB noise condition. Furthermore, we assessed neurobehavioral function and observed the level of neuroinflammatory response and blood–brain barrier (BBB) integrity in the hippocampal region. The LPS-injected sepsis mouse model exposed to noise exhibited increased anxiety-like behavior and cognitive impairment. Moreover, severe neuroinflammation and BBB disruption were detected in the hippocampal region. This study provides insights suggesting that persistent noise exposure under systemic inflammatory conditions may cause cognitive dysfunction and anxiety- like behavior via the mediation of BBB disruption and neuroinflammation. As a result, we suggest that the detailed regulation of noise exposure may be required to prevent the development of postoperative delirium.