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Background Autoimmune encephalitis (AE) has emerged as a treatable cause of first episode psychosis (FEP). Despite growing evidence supporting antibody-mediated psychopathology, optimal approaches for identifying and managing these patients remain undefined. We evaluated the clinicopathological features in patients presenting with FEP and AE to establish evidence-based neuropsychiatric care pathways.Methods An initial cohort of 440 cases identified through ICD-10 diagnostic codes, 118 patients were included in the final study cohort (106 with FEP and 12 with AE) after applying exclusion criteria for secondary causes of neuropsychiatric presentations. Comprehensive clinical, serological, neuroimaging, and treatment response data were systematically analysed across both groups.Results AE patients exhibited a distinct demographic profile, being older and predominantly female, as compared with the FEP cohort. AE presentations were characterised by prominent neurological signs, fever, and memory deficits, while FEP patients predominantly exhibited primary psychotic symptoms such as delusions, thought disorder, and hallucinations. MRI abnormalities were noted in over half of AE patients, while the majority of FEP patients had normal neuroimaging. Symptom resolution was achieved in the majority of AE patients with immunotherapy and in most FEP patients with antipsychotic treatment. Hospital length of stay was significantly longer in the AE cohort.Conclusions Study highlights distinct clinicopathological characteristics of FEP and AE patients, with implications for diagnostic algorithms and therapeutic intervention. Targeted investigation of autoimmune aetiologies, guided by established neurological ‘red flags,’ may be more efficacious than universal screening. Findings support the development of stratified neuropsychiatric care pathways to optimise diagnostic accuracy and therapeutic outcomes.