Key PointsQuestionIs place of birth associated with the efficacy of whole-body hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries?FindingsIn this nested cohort study within a randomized clinical trial recruiting 408 neonates with moderate or severe HIE from 7 tertiary neonatal intensive care units in South Asia, whole-body hypothermia was not associated with reductions in brain injury measured by magnetic resonance biomarkers at age 2 weeks among neonates born at either a tertiary care center or other facilities.MeaningThese findings do not support the use of whole-body hypothermia for neonates with HIE in low- and middle-income countries.