Mild therapeutic hypothermia (MTH) consists in cooling the body temperature of a patient to between 32 and 34 °C. This technique helps to preserve tissues and neurological functions in multi-organ failure by preventing ischemic injury. Total liquid ventilation (TLV) ensures gas exchange in the lungs with a liquid, typically perfluorocarbon (PFC). A liquid ventilator is responsible for ensuring cyclic renewal of tidal volume of oxygenated and temperature-controlled PFC. Hence, TLV using the lung as a heat exchanger and PFC as a heat carrier allows ultra fast cooling of the whole body which can help improve outcome after ischemic injuries. The present study was aimed to evaluate the control performance and safety of automated ultrarapid MTH induction by TLV. Experimentation was conducted using the Inolivent-5.0 liquid ventilator equipped with a PFC treatment unit that allows PFC cooling and heating from the flow of energy carrier water inside a double wall installed on an oxygenator. A water circulating bath is used to manage water temperature. A feedback controller was developed to modulate inspired PFC temperature and control body temperature. Such a controller is important since, with MTH induction, heart temperature should not reach 28 °C because of a high risk of fibrillation. The in vivo experimental protocol was conducted on a male newborn lamb of 4.7 kg which, after anesthetization, was submitted to conventional gas ventilation and instrumented with temperature sensors at the femoral artery, oesophagus, right ear drum and rectum. After stabilization, TLV was initiated with fast automated MTH induction to 33.5 °C until stabilization of all temperatures. MTH could be reached safely in 3 minutes at the femoral artery, in 3.6 minutes at the esophagus, in 7.7 minutes at the eardrum and in 15 minutes at the rectum. All temperatures were stable at 33.5 ± 0.5 °C within 15 minutes. The present results reveal that ultra-fast MTH induction by TLV with Inolivent-5.0 is safe for the heart while maintaining esophageal and arterial temperature over 32.6 °C.