A 27-year-old man with a diagnosis of new onset refractory status epilepticus (NORSE) was treated with five anti-seizure drugs (ASDs) including clobazam, levetiracetam and topiramate. He received plasma exchange (PE) for presumed autoimmune etiology. Serum ASD levels were serially monitored in two sessions. Levels of clobazam, levetiracetam and topiramate were significant reduced by PE. Serum clobazam level dropped down to at least 85% and 75% of the baseline during and after the procedure respectively; levetiracetam dropped down to 83% and 83%; and topiramate dropped to 86% and 79%. The results may imply a theoretical risk of breakthrough seizure during PE due to low ASD levels.