Delayed neurological deterioration after hypoxia is uncommon. Here we report a case of reversible delayed leukoencephalopathy following intravenous heroin intoxication with hypoxia. A 42-year-old man presented disturbed consciousness and unstable hemodynamic status after intravenous heroin injection. He made a good initial recovery after infection control and hemodynamic support. But his neurological condition deteriorated later on and gradually progressed into akinetic mutism and generalized hypertonia within 3 weeks. Prominent leukoencephalopathy was disclosed by magnetic resonance imaging (MRI) of the brain. His general condition improved again in a few months and follow-up MRI revealed regression of the white matter lesion. Early diagnosis of delayed leukoencephalopathy with appropriate supportive treatment may be worthwhile as illustrated by the reported case.