Reactive oxygen species (ROS) generated by Nox2 oxidase are reported to contribute to infarct damage following cerebral ischemia-reperfusion. Here we have examined for the first time the role of Nox2 expression in outcomes following permanent focal cerebral ischemia. Ischemia was induced by middle cerebral artery filament occlusion (MCAO) for 24h in wild-type (WT) and Nox2(-/y) mice. Neurological deficit and the hanging wire test were assessed, and infarct and edema volumes were estimated using thionin-stained brain sections. Genetic deletion of Nox2 had no effect on any outcome measures at 24h after permanent MCAO. Our data therefore suggest that ROS production by Nox2 oxidase activity plays no significant role in the pathophysiology of cerebral ischemia in the absence of reperfusion.