The Orange County Health Care Agency (HCA) has confirmed the county’s first case of influenza for the 2021-2022 season. Influenza activity remains low in Orange County at this time, but there are concerns about a more severe influenza season given both the relative dearth of disease and low influenza vaccine uptake during 2020-2021 season. This season will be further complicated by the ongoing COVID-19 pandemic. Providers should be considering testing for both influenza virus and SARS-CoV-2 in patients presenting with acute respiratory illness, as a positive test for one does not preclude a positive test for the other. Vaccination remains the best way to prevent both influenza and COVID-19 disease.