Neonatal seizures are diagnostically challenging and predominantly electrographic-only. Multichannel video continuous electroencephalography (cEEG) is the gold standard investigation, however, out-of-hours access to neurophysiology support can be limited. Automated seizure detection algorithms (SDAs) are designed to detect changes in EEG data, translated into user-friendly seizure probability trends. The aim of this study was to evaluate the diagnostic accuracy of the Persyst neonatal SDA in an intensive care setting. Single-centre retrospective service evaluation study in neonates undergoing cEEG during intensive care admission to Great Ormond Street Hospital (GOSH) between May 2019 and December 2022. Neonates with <44 weeks corrected gestational age, who had a cEEG recording duration >60 minutes, whilst inpatient in intensive care, were included in the study. One-hour cEEG clips were created for all cases (seizures detected) and controls (seizure-free) and analysed by the Persyst neonatal SDA. Expert neurophysiology reports of the cEEG recordings were used as the gold standard for diagnostic comparison. A receiver operating characteristic (ROC) curve was created using the highest seizure probability in each recording. Optimal seizure probability thresholds for sensitivity and specificity were identified. Eligibility screening produced 49 cases, and 49 seizure-free controls. Seizure prevalence within those patients eligible for the study, was approximately 19% with 35% mortality. The most common case seizure aetiology was hypoxic ischaemic injury (35%) followed by inborn errors of metabolism (18%). The ROC area under the curve was 0.94 with optimal probability thresholds 0.4 and 0.6. Applying a threshold of 0.6, produced 80% sensitivity and 98% specificity. The Persyst neonatal SDA demonstrates high diagnostic accuracy in identifying neonatal seizures; comparable to the accuracy of the standard Persyst SDA in adult populations, other neonatal SDAs, and amplitude integrated EEG (aEEG). Overdiagnosis of seizures is a risk, particularly from cEEG recording artefact. To fully examine its clinical utility, further investigation of the Persyst neonatal SDA's accuracy is required, as well as confirming the optimal seizure probability thresholds in a larger patient cohort.