Delirium is a clinical syndrome characterized by disturbances in attention, awareness, and cognition, and is common in older people following major surgery. In contrast to dementia, which is by definition progressive and irreversible, delirium is acute and usually transient. At present, any causation of dementia by delirium is not proven, but evidence suggests delirium and dementia may affect each other in terms of brain vulnerability. Therefore, understanding factors that can predispose people to delirium may contribute to understanding and ultimately preventing cognitive impairment. In this Ph.D. thesis, we accessed samples and data from a post-operative delirium cohort based in Belfast. The aim was to understand the pathological processes underlying delirium from several perspectives by employing metabolomic profiling of cerebrospinal fluid (CSF) and plasma samples. The studies investigated: (i) the perioperative change in metabolites; (ii) the relationship between blood-brain barrier (BBB) disruption and metabolites; (iii) the association between inflammation/neurodegenerative markers and metabolites; (iv) CSF and plasma trace element concentrations relative to delirium; (v) Lastly because CSF is relatively understudied in the metabolomics field, we investigated the relative stability of metabolites in CSF when stored at -20 ֯C for 5 years. In conclusion, metabolomics is a rapidly evolving field of research and has the potential to improve our understanding of the central and peripheral changes underlying a person's susceptibility to delirium. For now, the diagnosis of delirium is based on clinical history and cognitive assessments. This thesis brings forward new information on these changes and supports their continued use in larger clinical cohorts of postoperative delirium.