This study aimed to compare magnetic resonance imaging (MRI) severity scores and in-hospital outcomes among neonates with perinatal hypoxic-ischemic encephalopathy (HIE) with and without exposure to sedation-analgesia (SA) during therapeutic hypothermia (TH).A single-center, retrospective cohort study of neonates with perinatal HIE undergoing TH between January 2010 and December 2020. Demographics, clinical characteristics, MRI scores, and in-hospital outcomes were compared between patients without SA exposure and those with SA use.Of the 131 neonates, 55 (42%) did not have SA exposure, and 76 (58%) had SA during TH. Groups were similar in birth weight, gestational age, and severity of HIE. A higher proportion of neonates in the SA group received inhaled nitric oxide (iNO, 39.4 vs. 2%,