Infective endocarditis (IE) is a life-threatening condition often manifesting as a multisystem disease; its heterogeneous features present a diagnostic challenge. We report two cases of IE masquerading as rare extracardiac complications: a splenectomised patient with a periarticular ankle abscess and acute encephalopathy; and a young man with a cutaneous vasculitis following a spontaneous intracerebral haemorrhage. In both cases, the diagnosis was suspected following detection of afebrile bacteraemia and confirmed with echocardiography. Risk factors included a pneumococcal bacteraemia in the asplenic patient and a previously undiagnosed bicuspid aortic valve in the second patient. Both patients recovered well with appropriate antibiotic therapy followed by valve surgery. IE is an important diagnosis to consider in patients with systemic symptoms or organ specific, otherwise unexplained relevant pathology especially in the presence of a cardiac murmur or risk factors for IE including structural heart disease, prosthetic valves or intravascular devices, and in immunosuppressed patients.