Background: Patients in cardiogenic shock undergoing ECLS/ECMO therapy with peripheral cannulation are at risk of Harlequin syndrome. Symptoms can vary according to the level of the watershed. Case description: 49-year-old male receiving ECMELLA therapy after suffering from cardiogenic shock following a large anterior STEMI experiencing symptoms of Harlequin syndrome due to a large descending aortic thrombus perioperatively before receiving LVAD therapy. Medical therapy was successfully inducted. Conclusion: Although rarely seen, Harlequin syndrome can have severe clinical implications and mimic malperfusion. Treatment can be crucial in patients receiving LVAD therapy as complications affect morbidity and survival.