Background: More than 1 in 4 children admitted to the pediatric ICU (PICU) have suspected neuroinflammation for a variety of reasons. While often beneficial, uncontrolled inflammation can lead to secondary neurologic injuries and interfere with repair mechanisms. Methods: A prospective cohort study was initiated at Alberta Children’s Hospital to evaluate neuroinflammation in children admitted to the PICU. Forty-eight cytokines, chemokines and growth factors collected at multiple pre-determined timepoints were analyzed along with data on clinical trajectory. Preliminary exploratory analyses of patients enrolled January 2022-July 2023 were completed. Results: Fifty-three patients were included in the initial analysis. Encephalopathy (18.9%), hypoxia (17%) and TBI (15.1%) were the most common reasons for enrollment. All groups had temporal alterations in serum cytokines, with primary inflammatory brain diseases having the highest levels of innate inflammation (cytokine storm) on admission and day one compared to other subgroups. There was a trend towards normalization of cytokine levels over time. Conclusions: Temporal profiling of cytokine levels can inform on neuroinflammatory pathways contributing to the clinical course in critically ill children. Further analysis is ongoing with the entire cohort to evaluate longitudinal and between-group differences. Improved understanding of altered neuroinflammatory pathways in this population may assist with rationalizing targeted immunotherapies to improve outcomes.