In a retrospective cohort study of 19,651 patients hospitalized in Denmark with confirmed COVID-19, influenza, or respiratory syncytial virus between 2019 and 2024, atypical bacterial co-infection was rare, identified in just 21 patients (0.1% of those tested). Despite this low prevalence, empirical clarithromycin was administered to 859 patients, and most patients with confirmed atypical co-infection did not receive early macrolide therapy. The findings do not support routine testing or empirical treatment for atypical bacterial pathogens in patients hospitalized with viral respiratory infections, except in selected high-risk clinical scenarios.