Epilepsy and syncope are sometimes difficult to differentiate, and they often occur together. We report here a unique case of severe neuromodulatory syncope associated with generalized epilepsy. A 24-year-old right-handed female with no remarkable history had her first epileptic seizure when she was 15 years old and was diagnosed with epilepsy. However, she had epileptic seizures or fainting spells every few months and was referred to Nara Medical Center at the age of 23 years. No obvious neurological abnormality was present, and no organic abnormality was found on head magnetic resonance imaging. The seizures were symmetrical generalized tonic-clonic seizures (GTCS) without aura, and the patient was unable to stand up for several hours after the seizure. Long-term video electroencephalogram monitoring revealed two types of seizures: (1) GTCS starting with generalized polyspikes and waves and (2) fainting with sinus arrest for up to 10 seconds when the patient tried to stand up after GTCS. After the addition of valproic acid following the diagnosis of generalized epilepsy, her epileptic seizures improved, but syncope remained. We consulted the cardiology department of our hospital and diagnosed mixed neuromodulatory syncope after performing the tilt test. She underwent catheter ablation for cardioneuromodulation, and her syncope improved. Several reports have described reduced baroreflex sensitivity during the interictal period in epilepsy, and seizure-related autonomic dysfunction has been implicated in sudden unexpected death in epilepsy (SUDEP). In addition to suppression of epileptic seizures, when autonomic nervous system symptoms associated with epilepsy are severe, as in this case, a thorough cardiovascular examination should be performed, and the patient should be treated with the goal of preventing SUDEP.