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The progression of secondary pulmonary damage in SARS-COV-2 infection, associated with interstitial damage, inflammation and alveolar consolidation and eventually resulted in the development of pulmonary fibrosis (PF), remains one of the key clinical dilemmas for the treatment of patients in intensive care units (ICU). Currently, there is no standardized algorithm for PF prevention and timely management, although few studies have discussed the use of antifibrotic agents in COVID-19 patients. One of the treatment options for patients with interstitial PF, when irresponsive to the given corticosteroid therapy, is the administration of cytostatic agents, in particular, cyclophosphamide. Cyclophosphamide is one of the well-studied drugs in the cytostatic group, which effectiveness in inhibiting systemic inflammation suggests its ability to reduce the progression of the secondary lung damage, interstitial abnormalities and PF caused by the so-called "cytokine storm". The presented case reports provide data on the use of cyclophosphamide (Сy) in the management of severe respiratory failure in COVID-19 patients stationed in ICU. We describe three clinical cases characterized by different types of respiratory support, including extracorporeal membrane oxygenation. • Cyclophosphamide can be considered relatively safe and reasonably effective in severe lung damage in COVID-19. • Cyclophosphamide may reduce interstitial inflammation, thus preventing the development of pulmonary fibrosis. • No severe side effects were observed during low-dose cyclophosphamide therapy in our study [ABSTRACT FROM AUTHOR]