In patients with influenza-related myocarditis complicated by refractory cardiogenic shock (rCS) there is scarce evidence for mechanical circulatory support (MCS). We sought to investigate the impact of MCS using combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and micro-axial flow pumps in rCS complicating influenza-related myocarditis.This is a prospective and observational analysis from the single center Hannover Cardiac Unloading REgistry (HACURE) from two recent epidemic influenza seasons. We analysed patients with verified influenza virus infection-associated myocarditis complicated by rCS admitted to our ICU on MCS. Subsequently, we performed a propensity score matched analysis to patients with acute myocardial infarction complicated by rCS and non-ischemic cardiomyopathy related rCS.We describe a series of seven patients with rCS complicating influenza-related myocarditis (mean age: 56±10 years, 58% males, Influenza A/B n=2/5). No patient had been vaccinated prior to the influenza season. MCS was provided using combined VA-ECMO and Impella. In two patients with out-of-hospital cardiac arrest VA-ECMO had been implanted for extracorporeal-cardiopulmonary resuscitation. All patients died within 18 days after hospital admission. By propensity score-based comparison to patients with myocardial infarction- or non-ischemic cardiomyopathy related rCS with combined MCS, 30-day mortality was significantly higher in influenza-related rCS.Despite initial stabilisation with combined MCS in patients with rCS complicating influenza-related myocarditis, the detrimental course of shock could not be stopped and all patients died. Potentially, influenza virus infection critically affects other organs besides the heart leading to irreversible end-organ damage, which MCS cannot compensate and, therefore, resulted in a devastating outcome.