OBJECTIVES: This study sought to determine whether SARS-CoV-2 is present in the middle ear fluid (MEF) of patients with COVID-19 who have otitis media with effusion (OME). METHODS: A case-control study was designed to detect SARS-CoV-2 and six other common respiratory viruses (influenza A virus, influenza B virus, respiratory syncytial virus, adenovirus, human rhinovirus [HRV], and mycoplasma pneumonia) by polymerase chain reaction (PCR) in the MEF of patients with OME. Follow-up tests, including pure-tone audiometry and tympanometry, were conducted. RESULTS: In the COVID-19 group, 18 of 27 MEF specimens were PCR-positive for SARS-CoV-2, with cycle thresholds ranging from 24.9-42.2. And one patient tested positive for the HRV. In the control group, all 15 MEF specimens were PCR-negative for SARS-CoV-2, but two patients tested positive for the HRV. After treatment for OME, 11 patients (40.7%) reported complete resolution, 14 (51.9%) reported improvement, and two (7.4%) reported no change. The average improvement in hearing was 14.5 +/- 8.1 dB, and the average air-bone gap decrease was 13.5 +/- 9.0 dB. CONCLUSION: This study confirmed the presence of SARS-CoV-2 in the MEF of patients who were previously COVID-19-positive suggesting a possible association between COVID-19 and OME. OME should be considered a possible symptom of COVID-19.