Feline HCM is the most common cardiac disease in cats and has a complex and not fully elucidated pathophysiology. An initial chronic, low-grade inflammation, characterised by increased levels of pro-inflammatory cytokines, inflammatory cell infiltrates and, often, increased fibrosis occurs, but the initiating factor/s that trigger this early and sustained low grade inflammation are currently unknown. This study compared the plasma proteome of cats diagnosed with fHCM disease using SWATH MS proteomics with the aims to identify novel biomarkers for fHCM and to further elucidate disease pathogenesis. A total of 20 cats were enrolled in this study in two groups ie., healthy control (n=10), and HCM (n=10) respectively. Cats in HCM group, were diagnosed by echocardiography procedure and disease status was determined by a registered veterinary cardiologist. Following proteomic analysis, majority of the dysregulated proteins were associated innate and humoral response including complement C7, C9, and properdin proteins suggesting complement activation plays a vital role in HCM. Other dysregulated proteins were involved in blood coagulation including fibrinogen, fibulin -1; proteins associated with lipid metabolism, inflammation and extracellular matrix remodelling including apolipoprotein M, angiotensin-converting enzyme, transthyretin, plasminogen. These findings may provide an additional tool for diagnosis and insights of pathophysiological changes in fHCM