Background: Hypoxic-Ischemic Encephalopathy (HIE) is a type of neonatal encephalopathy where mortality rate is estimated by 11.2%, globally. The only known management for HIE is therapeutic hypothermia. However, many drawbacks have been associated with therapeutic hypothermia including death. Objective: Recording complications of treatment of hypoxic ischemic neonates using therapeutic hypothermia (TH) for improvement of the results of the management using TH. Patients and Methods: In this case-series study, which was conducted at the Neonatal Intensive Care Unit (NICU) of Mataria Teaching Hospital (MTH), Cairo, Egypt. The study was conducted from January 2018 to December 2019. All medical files of fourteen neonates presented with HIE and treated with hypothermia were reviewed. Results: Among the 14 neonates with HIE, survivor cases were 71.6%. They were discharged on single oral anticonvulsant and was weaned off after one month and all were on full oral feeding. One case died on second day of hypothermia due to severe pulmonary hypertension and uncontrolled hypotension (7.1%) and 21.3% had sepsis and 7.1% had early onset and died on 4^th day with maternal history of chorioamnionitis and 14.3% died from late onset sepsis. Conclusion: Although therapeutic hypothermia is a well-established treatment to neonates with hypoxic ischemic disease, their short-term effects can be easily controlled but low incidence of devastating complication can occur. Further controlled studies are needed to detect the factors associated with the elevated risk of such consequences.