The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in an unprecedented challenge to our healthcare system. Secondary and concurrent bacterial and viral co-infections are well documented for other viral respiratory pathogens; however knowledge regarding co-infections in COVID-19 remains limited. In the present study, concurrent testing of 50 419 individual samples for the presence of SARS-CoV-2 and other bacterial and viral respiratory pathogens was performed between March and August 2020. Overall, a lower rate of viral co-infection was observed in the SARS-CoV-2-positive population when compared to the population testing negative for the virus. Significant levels of Staphylococcus aureus and Epstein–Barr virus co-infections were detected in the SARS-CoV-2-positive population. This is one of the largest surveys looking into the co-infection patterns of SARS-CoV-2 infection in the United States. Data from this study will enhance our understanding of the current pandemic and will assist clinicians in making better patient care decisions, especially with respect to antimicrobial therapy.