BACKGROUND: The role of bacterial and viral co-infection in the current COVID-19 pandemic remains elusive. The aim of this study was to describe the rates and features of co-infection on admission of COVID-19 patients, based on molecular and routine laboratory methods. METHODS: A retrospective study of COVID-19 and non-COVID-19 patients undergoing Biofire((R)), FilmArray((R)) Pneumonia Panel, bioMerieux, and routine cultures during the first 3 days from admission, between June 2019 and March 2021. RESULTS: FilmArray tests were performed in 115 COVID-19 and in 61 non-COVID-19 patients. Most (>99%) COVID-19 patients had moderate-critical illness, 37% required mechanical ventilation. Sputa and endotracheal aspirates were the main samples analyzed. Positive FilmArray tests were found in 60% (70/116) of the tests amongst COVID-19 patients and 62.5% (40/64) amongst non-COVID-19 patients. All 70 cases were positive for bacterial targets, while one concomitant virus (Rhinovirus/Enterovirus) and one Legionella spp. were detected. The most common bacterial targets were Haemophilus influenzae (36%), Staphylococcus aureus (23%), Streptococcus pneumoniae (10%) and Enterobacter cloacae (10%). Correlation between FilmArray and cultures was found in 81% and 44% of negative and positive FA tests, respectively. Positive FilmArray results typically (81%) triggered the administration of antibiotic therapy and negative results resulted in antimicrobials to be withheld in 56% of cases and stopped in 8%. Bacterial cultures of COVID-19 patients were positive in 30/88 (34%) of cases. CONCLUSIONS: Bacterial co-infection is common amongst moderate-critical COVID-19 patients on admission while viral and atypical bacteria were exceedingly rare. Positive FilmArray results could trigger potentially unnecessary antibiotic treatment.KEY POINTWe found high rates of on-admission bacterial co-infection amongst hospitalized moderate to severe COVID-19 patients. Molecular tests (Biofire, FilmArray) and routine microbiological tests revealed 60% and 34% bacterial co-infection, respectively, while viral and fungal co-infections were rare.