Epilepsy is one of the most common neurological disorders globally, affecting about 50 million people, with nearly 80% of those affected residing in low- and middle-income countries. It is characterized by recurrent seizures that result from abnormal electrical brain activity, with seizures varying widely in manifestation. The exploration of the biomechanical effects that seizures have on brain dynamics and stress levels is relevant for the development of more effective treatments and protective strategies. This study uses a blend of experimental data and computational simulations to assess the brain’s physical response during seizures, particularly focusing on the behavior of cerebrospinal fluid and the resulting mechanical stresses on different brain regions. Notable findings show increases in stress, predominantly in the posterior gyri and brainstem, during seizures and an evidence of brain displacement relative to the skull. These observations suggest a dynamic and complex interaction between the brain and skull, with maximum shear stress regions demonstrating the limited yet essential protective role of the CSF. By providing a deeper understanding of the mechanical changes occurring during seizures, this research supports the goal of advancing diagnostic tools, informing more targeted treatment interventions, and guiding the creation of customized therapeutic strategies to enhance neurological care and protect against the adverse effects of seizures.