Background: Mitral valve disease (MVD) is a leading cause of atrial fibrillation (AF) and carries a risk of stroke. In the absence of valve disease, AF is linked to a hypercoagulable state with abnormalities such as platelet activation (soluble P-selectin (sPsel), and soluble CD40). An additional pathophysiological process is oxidized low-density lipoprotein cholesterol (oxLDL). However, data on hypercoagulability in AF on a background of valve disease is scarce. We therefore hypothesised altered sPsel, sCD40 and oxLDL in mitral valve disease with further abnormalities in the presence of AF. Method: We recruited 45 patients with valve disease of whom 24 were in sinus rhythm (VD-SR) and 21 were in AF (VD-AF), and 20 healthy controls (HC). sP-sel, oxLDL and CD40 by ELISA. Results (Table 1): Compared to HCs, sPsel was equally higher in VD-SR and in VD-AF (p0.001). sCD40 and oxLDL were higher in VD-AF than in HCs and VD-SR (both p0.001). Conclusion: Increased platelet activation is present in mitral valve disease but is not enhanced by AF. Increased sCD40 and oxLDL are features of AF, not of valve disease. These findings may have implications for the pathophysiology and management of these diseases.Finally, increased CD40 and oxLDL are a feature of AF, not of sinus rhythm. We believe these data provide new perspectives on the pathophysiology of AF and MVD.