Background: Hypocalcemia is a common morbidity in asphyxiated infants. Therapeutic hypothermia (TH), the standard of care for infants with moderate and severe hypoxic-ischemic encephalopathy (HIE), promotes neuroprotection by several mechanisms including a decrease in intracellular calcium (Ca2+) influx which may improve serum Ca2+ levels and homeostasis. Aims: To evaluate the impact of TH on Ca2+ homeostasis. Study design: Historical, retrospective cohort analysis. Subjects: Infants with moderate or severe HIE admitted to the hospital with 24 hours of age, gestational age 36 weeks, and birth weight >= 1800 g, before (pre-TH) and after (post-TH) TH was implemented. Outcome measures: Minimum and maximum serum levels of ionized Ca2+ (iCa(2+)) and magnesium (Mg), Ca2+ and Mg intakes, and incidence of hypo/hypercalcemia during the first week of life. Results: A total of 67 infants were included: 29 pre-TH and 38 post-TH. Minimum iCa(2+) levels were significantly lower in the pre-TH group; some infants required Ca2+ boluses infusions. In the post-TH group, a significantly lower intake of Ca2+ was necessary to maintain normal Ca2+ levels and no infant required boluses. The incidence of hypocalcemia was higher in the pre-TH group with a statistically significant difference on day 2 of life (18 vs 0%; p = 0.01). Conclusions: After the implementation of TH, iCa(2+) levels were within normal ranges despite lower Ca2+ intakes. A lower incidence of hypocalcemia was observed during cooling. Our findings support the hypothesis that TH improves Ca2+ homeostasis in HIE infants. (C) 2015 Elsevier Ireland Ltd. All rights reserved.