SUMMARY Cancer cachexia is a complex metabolic syndrome characterized by muscle wasting, weight loss, and decreased quality of life. Patients with cancer cachexia experience impaired muscle function, reduced treatment tolerance, and lower survival rates. Despite progress in understanding the condition, its underlying mechanism and high mortality rate remain unclear. The proposed research aims to investigate the role of platelets in cancer cachexia development, as they are involved in inflammation and tissue wasting. Preliminary data suggest an association between elevated platelet counts and the pre-cachexia stage and platelet activation and severe/refractory cachexia. The proposed study hypothesizes that platelets play a crucial role in the recruitment of immune cells and the release of pro-cachectic factors, ultimately leading to muscle loss. The research will test the hypothesis through two aims: depleting platelets at pre-cachectic stages to assess the impact on inflammation and muscle wasting and examining the effects of activated platelets on muscle wasting in cancer and chemotherapy-induced cachexia. The project aims to provide novel insights and potential approaches by targeting platelets in cancer cachexia.