Respiratory failure and systemic inflammation are paramount features of severe SARS-CoV-2 disease (COVID-19). Extracorporeal membrane oxygenation (ECMO) therapy has a potential role in patients with refractory disease. An inflammatory response due to blood contact with hemofilters, functioning as a synergic inflammatory stimulus, can lead to a hyperinflammatory state, relatable to cytokine release syndromes. After the first patient succumbed to a refractory vasodilatory shock believed to be due to hyperinflammatory state, a strategy of blood purification through cytokine adsorption therapy (CAT) with CytoSorb® was designed. In this case series, the authors describe the initial experience with such strategy. CAT was employed with no direct complications and helped controlling the inflammatory state, with all patients halting vasopressor support in 72 h and biomarker levels (C-reactive protein, ferritin, and interleukin-6) showing negative trends in most patients. Analysis of inflammatory biomarkers evolution highlighted 2 biomarker profiles related to the presence or absence of superinfection at the time of CAT implementation. In this case series of severe COVID-19 patients, 3 patients died – irreversible lung fibrosis, complications of critical hypoxemia before ECMO induction and complications of systemic anticoagulation were the causes. This case series aimed to contribute to the body of evidence substantiating CAT utilization in hyperinflammatory patients, namely, COVID-19 patients requiring ECMO rescue.