Objectives To investigate the changes of serum monoamine neurotransmitters and myocardial enzymes in patients with refractory epilepsy (RE), and the possible effects on the cardiovascular system, which would contribute to provide help and guidance to the early warming and prevention to the sudden unexpected death in epilepsy (SUDEP). Methods We collected sixty patients with RE who admitted to Neurological department of First Hospital of Jilin University from December 2015 to December 2016. According to the exclusion criteria, we selected thirty-two patients into the study. The study included 21 males and 11 females patients. Epinephrine (EPI), norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), creatine kinase isoenzyme (CKMB), lactate dehydrogenase (LDH) and hydroxybutyrate dehydrogenase (HBDH) were measured in peri-ictal period and the interictal period in the patients. All the data were analyzed by SPSS17.0 statistical software. Results ① Thirty two patients were eligiblefor this study and the maleto female ratio is 21:11; The age ranged from 15 to 85 years old, with the average age of 50.9±17.6 years old. Twelve (37.5%) were older than 60 years old and 20 (62.5%) were under 60 years old. The epilepsy history ranged from 1 year to 14 years, with an average of 3.75±3.12 years; ② Comparing the levels of monoamine neurotransmitters in peri-ictal period and the interictal period in the patients with RE, we found that the level of EPI and LDH was significantly lower than that in interictal period, while the levels of NE and DA were significantly increased; ③ The results showed that EPI, NE and DA levels in patients under 60 were higher than over 60; ④ Patients were divided into four groups according to the etiology of the disease: idiopathic epilepsy group (10 cases, 31.25%), post-encephalitic epilepsy group (7 cases, 21.88%), post-stroke epilepsy group (9 cases, 28.12%) and epilepsy after brain injury group (6 cases, 18.75%). The results showed that the levels of EPI, NE and DA in the post-strokeepilepsy group were significantly lower than those in the other three groups. The level of CKMB in the idiopathic epilepsy group was higher than that in post-stroke epilepsy and epilepsy induced by brain injury patients. Conclusions RE patients have a higher level of serum NE and DA interictal period, suggesting that seizures may increase sympathetic nervous excitability. The patients under 60 years-old with RE release more catecholamines than young patients, suggesting that the latterwith intractable epilepsy may have higher sympathetic nerve excitability. And it may be associated with the higher incidence of SUDEP in young patients. Post-stroke epilepsyrelease less catecholamine than others, suggesting that the sympathetic nervous excitability is relatively low, and it may have relatively little damage to heart.