Abstract Background Epilepsy is a multifaceted chronic neurological disease characterized by recurrent spontaneous seizures. It affects almost 70 million patients around the globe, making it one of the most common chronic causes of neurological morbidities. Aim of the Work detect an association between some inflammatory markers {C-reactive protein (CRP), Neutrophil-lymphocyte ratio (NLR), and Platelet-lymphocyte ratio (PLR)}and epilepsy in order to detect a pathogenic relation that in turn can influence the course and management of epilepsy. Patients and Methods the current body of evidence recognizes the association between inflammation and epilepsy. Several inflammatory markers have been investigated in relation to different types of epilepsy. This study chose CRP as a convenient and widely used inflammatory marker, together with NLR and PLR, the two novel, readily available indices of inflammation that are yet to be fully investigated in relation to epilepsy. We included 50 patients with uncontrolled generalized motor tonic–clonic seizures. Ages ranged from 18 – 45 years and both genders were represented. Patients were compared with 50 controls of same age and gender. Strict inclusion and exclusion criteria were applied to all volunteers. Results In this study, levels of CRP, NLR and PLR in 50 patients with epilepsy were significantly higher than controls. These results add to the pool of evidence that support the association between epilepsy and inflammatory processes. This study managed to investigate the correlation between inflammatory markers and specific independent variables such as frequency of seizures, time interval between last seizure and presentation, number of status epilepticus per year, number of anti-epileptic medications, duration of postictal confusion, age of onset of seizures, duration of illness, and EEG findings, in addition to age and gender differences. This study found increased levels of CRP, NLR, and PLR in patients with high frequency seizures compared to those with intermittent seizures. Similar results were obtained with increased number of episodes of status epilepticus, number of anti-epileptic medications and shorter time interval between last reported seizure and sample withdrawal. Longer duration of postictal confusion was associated with high values of NLR and PLR. Conclusion systemic inflammatory response has been detected in patients with uncontrolled generalized motor tonic–clonic seizures, which confirms the association between inflammation and epilepsy. This association is specifically correlated to higher seizure frequency, shorter duration between last seizure and blood sample withdrawal, higher number of status epilepticus in the last 12 months, higher number of anti-epileptic medications, longer duration of post-ictal confusion and female gender.