Permanent focal brain damage can have critical effects on the function of nearby as well as remote brain regions. However, the effects of transient disturbances on global brain function are largely unknown. Our goal was to develop an experimental in vivo model to map the impact of transient functional brain impairment on large-scale neural networks in the absence of structural damage. We describe a new rat model of transient functional hemispheric disruption using unilateral focal anesthesia by intracarotid pentobarbital injection. The brain's functional status was assessed with resting-state fMRI (rs-fMRI) and electroencephalography (EEG). We performed network analysis to identify and quantify highly connected network hubs, i.e., “rich-club organization,” in pre- and postbarbital functional networks. Perfusion MRI data demonstrated that the catheterized carotid artery predominantly supplied the ipsilateral hemisphere, allowing for selective hemispheric brain silencing. The prebarbital baseline network displayed strong functional connectivity (FC) within and between hemispheres. Following pentobarbital injection, the disrupted hemisphere revealed increased intrahemispheric FC with concomitant decrease of interhemispheric connectivity. The bilateral functional network was characterized by a strong positive rich-club effect, which was not affected by ipsilateral disruption. Nevertheless, the rich-club value was significantly decreased in the ipsilateral hemisphere and to a lesser extent contralaterally. Loss of interhemispheric EEG synchronization supported the rs-fMRI findings. Our data support the concept that densely connected rich-club regions play a central role in global brain communication, and show that network hub configurations can be significantly affected by focal temporary functional hemispheric disruption without structural neuronal damage. Further studies with this rat model will provide essential additional insights into network reorganization patterns in response to transient functional brain disruption.