Smoke inhalation is the most common cause of acute cyanide poisoning in the developed world. Hydroxocobalamin is an antidote for cyanide poisoning. There is little published about human intraosseous antidote administration. We present a case of intraosseous hydroxocobalamin administration in an adult smoke inhalation victim, found in cardiac arrest inside her burning manufactured home. Return of spontaneous circulation was achieved after 20 min of cardiopulmonary resuscitation. Five grams of hydroxocobalamin were subsequently given intraosseously. On hospital arrival, patient was found to have a respiratory-metabolic acidosis. She had red-coloured urine without haematuria, a known sequela of hydroxocobalamin administration. Patient’s neurological status deteriorated, and she died 4 days after admission. This case highlights that intraosseously administered hydroxocobalamin seems to adequately flow into the marrow cavity and enter the circulatory system despite the non-compressible glass antidote vial. This appears to be only the second reported human case of intraosseous hydroxocobalamin administration.