Invasive fungal disease (IFD) is associated with the mortality of patients on extracorporeal membrane oxygenation (ECMO). Several risk factors for IFD have been identified in patients with or without ECMO. Here, we assessed the relevance of coronavirus disease (COVID-19) for the occurrence of IFD in patients on veno-venous (V-V) ECMO for respiratory failure. In a retrospective analysis of all ECMO cases between January 2013 and December 2022 (2020–2022 for COVID-19 patients), active COVID-19 and the type, timing and duration of IFD were investigated. Demographics, hospital, ICU length of stay (LoS), duration of ECMO, days on invasive mechanical ventilation, prognostic scores (Respiratory ECMO Survival Prediction (RESP) score, Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS)-10, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score (SAPS)-II) and length of survival were assessed. The association of COVID-19 with IFD was investigated using propensity score matching and uni- and multivariable logistic regression analyses. We identified 814 patients supported with ECMO, and 452 patients were included in further analyses. The incidence of IFD was 4.8% and 11.0% in patients without and with COVID-19, respectively. COVID-19 status represented an independent risk factor for IFD (OR 4.30; CI 1.72–10.85; p: 0.002; multivariable regression analysis). In patients with COVID-19, 84.6% of IFD was candidemia and 15.4% represented invasive aspergillosis (IA). All of these patients died. In patients on V-V ECMO, we report that COVID-19 is an independent risk factor for IFD, which is associated with a detrimental prognosis. Further studies are needed to investigate strategies of antifungal therapy or prophylaxis in these patients.