Acute respiratory and neurologic disease after smoke inhalation are well documented, but human patients may also develop delayed-onset neurologic symptoms associated with leukoencephalomalacia after exposure to smoke or carbon monoxide. In this case, a dog developed progressive neurologic signs 6 days after rescue from an apartment fire. At necropsy 9 days after smoke inhalation, leukoencephalomalacia of the central cerebral white matter was accompanied by laminar necrosis of cerebrocortical neurons. This is the first report of delayed posthypoxic leukoencephalopathy in a nonhuman animal.