The pathophysiological characteristics of sepsis in striated muscle tissues are the potential key to identifying the regulatory factors of sepsis and establishing a molecular basis for drug discovery. Arrhythmia is a major cause of septic death. The cardiac IKs channel is regulated by intracellular Ca²⁺, cAMP, and NO, which are increased during sepsis. Transgenic mice expressing cardiac IKs channel (IKs-TG mice) were significantly tolerant to a cecal slurry injection-induced sepsis in viability and cardiac anomalies. Our membrane proteomic analysis showed the interaction KCNQ1 interacts with Na-Ca exchanger (NCX1), which is involved in Ca²⁺ overload during sepsis, in isolated ventricular myocytes from IKs-TG mice. These suggest that the IKs channel participates in a compensatory response to sepsis, involving interaction between KCNQ1 and NCX1. Skeletal muscle is also a striated muscle tissue response to sepsis. Recent reports suggested muscular septic responses is a key to the high tolerance of sepsis in female. Cecal ligation and puncture-induced septic symptoms in Four Core Genotypes (FCGs) mice (XX gonadal males or females, and XY gonadal males or females) showed that XX female mice were significantly resistant among FCGs to septic death. Our RNA-seq analysis in skeletal muscle of septic FCGs revealed that four inflammation-related genes were overexpressed specifically in XX females. Our analysis of sepsis pathophysiology in cardiac and skeletal muscle has led to the detection of new molecular targets involved in sepsis symptoms.