Background <p>Automated pupillometry is a novel technology which can measure pupillary dynamics objectively at the bedside in critically ill patients. The Neurologic Pupil Index (NPi), a composite metric derived from pupillary reactivity parameters, has been proposed as a more objective measure of pupillary function and a potential prognostic tool in neurocritical illness. We hypothesized that the minimum NPi (NPi_min) measured in critically ill children would correlate with functional outcome at hospital discharge.</p> Methods <p>This was a single-center retrospective observational cohort study of patients admitted to the pediatric intensive care unit (PICU) with primary brain injury or risk of secondary brain injury. The NPi_min reported during the PICU admission was compared with measures of outcome. Unfavorable outcome was defined by death or a change in functional status scale (FSS) score of ≥ 3 points from baseline to hospital discharge, whereas favorable outcome was alive and change in FSS score &lt; 3).</p> Results <p>Automated pupillometry data were extracted from one-hundred and six patients, 77 (72.6%) of whom had a primary neurologic diagnosis and 25.5% of whom died. The NPi_min was significantly lower in children who experienced an unfavorable outcome compared to those with a favorable outcome (0.8 vs. 3.7; p &lt; 0.001). Prognostic performance of NPi_min for unfavorable outcome was assessed using logistic regression which demonstrated an area under the receiver operative curve (AUROC) of 0.82 and optimal NPi_min threshold of ≤ 2.1. When patients with an NPi_min of 0 were excluded, NPi_min best predicted unfavorable outcome at a higher NPi threshold of ≤ 3.5 with an AUROC of 0.72.</p> Conclusion <p>Minimum NPi values were strongly associated with functional outcome at hospital discharge in a single-center cohort of critically ill children. Further research may reveal a role for NPi as an objective bedside biomarker that could enhance pediatric-specific prognostic models.</p>