Subcutaneous fat necrosis (SCFN) of the newborn is a form of panniculitis that affects full-term neonates who often have suffered either birth asphyxia or hypothermia. The induction of hypothermia in newborns is becoming frequently used to reduce the neurologic sequelae associated with birth asphyxia. The risk of SCFN in neonates undergoing this therapy is unknown. Observation We describe a neonate who developed an abscess-like presentation of SCFN and subsequent asymptomatic hypercalcemia after undergoing whole-body cooling for hypoxic-ischemic encephalopathy. Hypothermia protocols may be placing newborns at increased risk for the development of SCFN. Clinicians should recognize this association, and newborns who undergo therapeutic cooling should have frequent dermatologic assessments.