With the onset of the COVID-19 pandemic, it became apparent that, in addition to pulmonary infection, extrapulmonary manifestations such as cardiac injury and acute cerebrovascular events are frequent in patients infected with SARS-CoV-2, worsening clinical outcome. We reviewed the current literature on the pathophysiology of cardiac injury and its association with acute ischaemic stroke. Several hypotheses on heart and brain axis pathology in the context of stroke related to COVID-19 were identified. Taken together, a combination of disease-related coagulopathy and systemic inflammation might cause endothelial damage and microvascular thrombosis, which in turn leads to structural myocardial damage. Cardiac complications of this damage such as tachyarrhythmia, myocardial infarction or cardiomyopathy, together with changes in hemodynamics and the coagulation system, may play a causal role in the increased stroke risk observed in COVID-19 patients. These hypotheses are supported by a growing body of evidence, but further research is necessary to fully understand the underlying pathophysiology and allow for the design of cardioprotective and neuroprotective strategies in this at risk population.