Background <p>Megakaryocytes are traditionally recognized as cells responsible for platelet production. However, beyond their role in thrombopoiesis, megakaryocytes also participate in inflammatory responses and regulate immune system functions. Sepsis, characterized by life-threatening organ dysfunction due to a dysregulated response to infection, prominently features coagulopathy, severe inflammation, and immune dysfunction as key pathophysiological aspects.</p> Aim of review <p>Given the diverse functions of megakaryocytes, we explore their roles in coagulation in the context of sepsis, and also in inflammatory and immune regulation. We try to infer future research directions and potential strategies for sepsis prevention and treatment based on the properties of megakaryocytes.</p> Key scientific concepts of review <p>The purpose of this review is to both highlight and provide an update on the functions of megakaryocytes and pathophysiological changes in sepsis. Specific emphasis is given to the role of megakaryocytes in sepsis, which suggests value of future research and clinical application.</p> Graphical abstract <p></p>