Nerve agents are highly toxic chemicals that pose an imminent threat to soldiers and civilians alike. Nerve agent exposure leads to an increase in acetylcholine within the central nervous system, resulting in development of protracted seizures known as status epilepticus (SE). Currently, benzodiazepines are the standard of care for nerve agent-induced SE, but their efficacy quickly wanes as the time to treatment increases. Here, we examine the role of the α2-adrenoceptor in termination of nerve agent-induced SE using the highly specific agonist dexmedetomidine (DEX). Adult male rats were exposed to soman and entered SE as confirmed by electroencephalograph (EEG). We observed that administration of DEX in combination with the benzodiazepine midazolam (MDZ) 20 or 40 min after the onset of SE stopped seizures and returned processed EEG measurements to baseline levels. The protective effect of DEX was blocked by the α2-adrenoceptor antagonist atipamezole (ATI), but ATI failed to restore seizure activity after it was already halted by DEX in most cases, suggesting that α2-adrenoceptors may be involved in initiating SE cessation rather than merely suppressing seizure activity. Histologically, treatment with DEX + MDZ significantly reduced the number of dying neurons as measured by FluoroJade B in the amygdala, thalamus, and piriform cortex, but did not protect the hippocampus or parietal cortex even when SE was successfully halted. We conclude that DEX serves not just as a valuable potential addition to the anticonvulsant regimen for nerve agent exposure, but also as a tool for dissecting the neural circuitry that drives SE.