Acute respiratory distress syndrome (ARDS) is a condition affecting 10% of patients requiring admission to the intensive care unit and results from endothelial dysfunction, alveolar epithelial injury and unbalanced inflammation, leading to exudative pulmonary oedema. A significant portion of these patients experience a lung injury that fails to resolve. Persistent or worsening respiratory failure beyond 5 days after the initiation of mechanical ventilation is referred to as nonresolving ARDS. Viral and fungal pathogens can exploit the hyperinflammatory environment and altered immune landscape in ARDS, perpetuating a cycle of ongoing inflammation and lung injury, thereby contributing to the progression towards and persistence of nonresolving ARDS, even in previously immunocompetent patients. This review discusses the significance, pathophysiology, diagnostic challenges and key knowledge gaps concerning various viral and fungal pathogens in nonresolving ARDS, with a particular focus on influenza-associated and COVID-19-associated pulmonary aspergillosis and pulmonary reactivation of