Background & Aims: Sleep and epilepsy are complex interactions and are completely interdependent, so that some patients experience seizures while asleep or deprived of sleep or when waking up, and for some they occur during the day or night (1). The American Psychiatric Association defines sleepiness as symptoms of excessive quantity of sleep (e.g., extended nocturnal sleep or involuntary daytime sleep), deteriorated quality of wakefulness (i.e., sleep propensity during wakefulness as shown by difficulty awakening or inability to remain awake when required), and sleep inertia (i.e., a period of impaired performance and reduced vigilance following awakening from the regular sleep episode or from a nap) (2). Its prevalence is higher in seizures than in the control group (3, 4) and in different groups seizures have been reported between 31 to 60% (5-7). According to common clinical beliefs, sleep disruption can have a significant effect on memory, as REM sleep or slow-wave sleep is essential for optimal cognitive function (3), and excessive daily sleepiness can increase seizures (8, 9) and pain (10) in patients; However, the exact function of sleep remains unclear, and the findings have not always been consistent. These discrepancies require the conduct of research in which, through a comprehensive look, a large number of parameters related to sleepiness are present in seizures. In other words, the heterogeneity of the previous findings highlights the variability of the course of the disease as a result of the interaction of sleepiness and seizures, which makes it necessary to conduct more research to better understand the problems of patients. Therefore, the aim of the present study was to investigate the comorbidity effect of sleepiness and epilepsy on cognitive functions, quality and severity of pain and disease severity markers in patients with epilepsy. Methods: The present research was conducted as a case-control study in 2020 in Shiraz Namazi Hospital. The statistical population of this study included all patients with focal epileptic seizures (temporal lobe epilepsy) (n = 30) and generalized (idiopathic generalized epilepsy) (n = 21) and psychogenic non-epileptic seizures (n = 17) in Shiraz. Through their follow-up treatment process, they referred to the epilepsy and seizure ward of Shiraz Namazi Hospital, from which 68 patients with inclusion criteria were selected through purposive sampling method. According to the inclusion and exclusion criteria, each patient completed a comprehensive list of demographic and clinical variables, the Stanford Sleepiness Scale, the Montreal Cognitive Assessment, the McGill Pain Questionnaire, and the Visual Analogue Scale under the supervision of an on-site clinical psychology PhD student. After collecting research data, patients with seizures were divided into two groups with sleepiness (n = 45) and no sleepiness (n = 23) through a cut score equal to or greater than 3 on the Stanford Sleepiness Scale. Data were analyzed using parametric and non-parametric tests in version 24 of SPSS software. Results: Preliminary findings showed that there was a significant difference between the two groups of patients with epilepsy with and without sleepiness in terms of mean age and frequency of antiepileptic drugs (P <0.05); While there was no difference between the two groups in terms of type of seizure, education, gender, marital status and employment status. In order to investigate the effect of sleepiness on cognitive function and components related to pain quality, multivariate and univariate analysis of covariance was used to control age variables and use antiepileptic drugs. The results showed that patients with sleepiness in functions of language, Abstraction, delayed recall, as well as achieving the overall Montreal Cognitive Assessment score performed worse. These patients had higher sensory perception of pain experience, rated their pain higher, scored higher in pain quality, and chose more words to describe their pain (P<0.05). Evaluations of disease severity markers through nonparametric tests also showed that compared to patients without sleepiness, patients with epilepsy with sleepiness have experienced more pain, more seizures, a higher incidence of comorbid physical diseases, a longer history of psychiatric diagnoses, and they have more concomitant use of antiepileptic and psychiatric drugs (P<0.05). Conclusion: The results showed that patients with epilepsy with sleepiness had lower mean scores on some cognitive subscales than their counterparts without sleepiness; However, the two groups did not differ in terms of spatial visual function, naming, attention, and orientation. Using a methodology similar to this study, Vascouto et al. Found that there was no difference between the two groups of patients with seizures with and without sleepiness in most cognitive components such as attention and spatial visual skills; Only from the point of view of the total score of auditory verbal learning, there is a significant difference (11) that is relatively consistent with the present study. Although more research is needed to draw more detailed discussions, the discrepancies in some findings can be explained by differences in the type of patient samples in the two studies and the reduction in attention and performance resulting from sleepiness. The results also showed that patients with epilepsy with sleepiness compared to their counterparts, evaluated the qualitative dimensions of their pain higher and experienced more severe pain. Consistent with these findings, Gutter et al. Found that sleepiness comorbidity in epileptic seizures leads to increased chronic pain in patients (10) and Jaussent et al. Also reported that chronic pain is a significant predictor of sleepiness (12). In this regard, potential underlying mechanisms such as structural and functional changes in the prefrontal cortex (13), anterior cingulate cortex (14), hippocampus (15), amygdala (16), insula (17), subcortical regions (17) and shock spinal cord passages (18); Neural-glial interactions; Abnormalities in autonomic function and hypothalamic-pituitary-adrenal axis and other biological factors may contribute to the relationship between sleepiness and pain. Finally, the results showed that the frequency of seizures, the presence of comorbidities of physical disease, the history of psychiatric diagnoses and the simultaneous use of antiepileptic and psychiatric drugs in patients with epilepsy with sleepiness were higher than their counterparts. In this regard, Pizzatto et al. (19) and Xu et al. (20) evaluated patients with epileptic seizures and did not find a relationship between daily sleepiness scores and the frequency of seizures. But Lee et al. Showed that the presence of psychiatric symptoms is an independent predictor of sleepiness in patients (21). It seems that sleepiness reduces the ability to control seizures in patients (22) and contributes to their recurrence and worsening of the disease. Disruption of patients' circadian rhythms can also be involved as a consequence of sleepiness; Because circadian rhythms affect the frequency of seizures depending on the epileptogenic region (23,24). According to the findings, measuring sleep habits, sleep hygiene and comorbidity of sleepiness is an unavoidable necessity. In particular, early diagnosis and treatment of comorbid sleepiness and seizures can improve the prognosis and reduce the negative health consequences in patients (25). Lack of objective measurements of sleepiness and self-reported nature of the data are the limitations of the present study. Future studies can complement these findings by using objective measures of sleepiness. Patients with epilepsy with sleepiness have a poorer cognitive and clinical status than their counterparts. [ABSTRACT FROM AUTHOR]