We investigated the effect of mild whole-body hyperthermia (40 °C) on a permanent middle cerebral artery occlusion (MCAo) model in Fisher rats by subjecting them to MCAo under the following conditions: (1) normothermia (n = 20); (2) hyperthermia (n = 14) before (1 hour), during, and after (1 hour) MCAo; and (3) post-MCAo hyperthermia (n = 14) for 1 hour. We measured brain and body temperatures during the experiment using micro-thermocouples and blood-brain-barrier (BBB) permeability using Evans blue staining of the brain. We measured the volume of the infarcted brain tissue 4 days after MCAo. We detected no differences in BBB permeability among three groups. The volume of infarcted tissue was significantly greater (p <0.05) for the two groups of hyperthermic animals than the normothermic animals. Our data suggest that mild hyperthermia, both during and after induction of ischemia, has a detrimental effect on the ischemic infarct volume in this model.