A cluster of coronavirus disease (COVID-19) cases occurred in a 40-bed private hospital in Oita City, Japan. This study examined the effect of heat and moisture exchangers (HMEs) with electrostatic filters on infection control. The study included 32 hospitalized patients, including four patients with normal breathing (non-tracheostomized patients), two tracheostomized patients with spontaneous breathing, and 26 tracheostomized patients on ventilators. HMEs without filters were used for airway management in the two tracheostomized patients with spontaneous breathing and one tracheostomized patient on ventilator, and HMEs with electrostatic filters were used in 25 tracheostomized patients on ventilators. All patients with negative test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen were further tested by reverse transcription polymerase chain reaction to confirm the absence of infection. All non-tracheostomized patients and tracheostomized patients with spontaneous breathing (100%) and two of the 26 (7.6%) tracheostomized patients on ventilators were confirmed to have SARS-CoV-2 infection. Both patients (100%) who used HMEs without filters were infected, whereas only one of the 25 patients (4%) using HMEs with electrostatic filters was infected, showing a significantly lower rate of infection in the latter group. The present results suggest that in situations where the level of virus contamination in the environment is high, such as during a large-scale COVID-19 outbreak, use of HMEs with electrostatic filters would be effective for controlling infection.