We report on a 47-year-old woman with autopsy proven Creutzfeldt-Jakob disease (CJD), who had a positive initial 14-3-3 test but a subsequent negative test under pharmacologic suppression of the periodic epileptiform discharges on EEG. Multiple factors associated with a subsequent 14-3-3 test becoming negative are known. However none of these circumstances were applicable to our patient. This case history suggests sedative therapy in CJD may induce false negative 14-3-3 testing. This appears to be a relevant finding, since the differential diagnosis between non-convulsive status epilepticus and CJD is not always evident in the initial stage of the disease and some patients with CJD present with seizures.