Infantile epileptic spasm syndrome (IESS) presents a significant challenge in pediatric neurology due to its potential for progressive cognitive and behavioral impairments. This study aimed to shed light on the pathogenesis of IESS through a comprehensive proteomic analysis of plasma samples using data-independent acquisition (DIA) methodology. This research was supposed to provide valuable insights into the pathogenesis of IESS and offers a basis for future studies focusing on personalized therapeutic approaches.