Introduction: hypoxic-ischemic encephalopathy is a clinical syndrome due to lack of perfusion and oxygen to the brain.One of the main risk factors for its development is perinatal infection, which also increases the risk of sepsis and worsens the patient's prognosis.Objective: to determine the relationship between sepsis and hypoxic-ischemic encephalopathy in patients undergoing regional brain hypothermic therapy.Methodology: retrospective, descriptive study of a cohort of newborns with hypoxicischemic encephalopathy subjected to brain hypothermic therapy for whom clinical, neurological and paraclinical variables for the study of sepsis were compared, and for which the probability of sepsis was estimated using the Phillips scale.Results: 85.7% of the patients presented some sentinel event, the most frequent being prolonged expulsion (55.6%).90% of the patients presented with moderate and severe Sarnat -Sarnat classification.65% of the patients received antibiotics and two patients had positive blood cultures.76.1% of the patients with blood cultures had negative results.Only two patients (3.1%) had a score of two on the Phillips scale.A relationship was found with respect to the outcome, with a p value of 0.16, and 0.175 between the Phillips score and the severity of the encephalopathy.The relationship between clinical severity according to the Sarnat-Sarnat scale and positive blood culture had a p value of 0.051. Conclusion:it is very difficult to determine the presence of infection with any degree of certainty in these patients because their pathological process behaves very similarly to sepsis and this, added to inflammatory mediators and physiological responses, make it difficult to predict the risk of sepsis using current scales.It is necessary to find markers that are more sensitive and specific for sepsis in neonates undergoing hypothermia in order to improve the decision-making process and its effects on the prognosis for these patients.