Background: The adoption of remote patient monitoring (RPM) in routine medical care requires increased understanding of the physiologic changes accompanying disease development and the proactive interventions that will improve outcomes. Objective: The aim of this study is to present three case reports that highlight the capability of RPM to enable early identification of viral infection with COVID-19 in patients with chronic respiratory disease. Methods: Patients at a large pulmonary practice who were enrolled in a respiratory RPM program and who had contracted COVID-19 were identified. The RPM system (Spire Health) contains three components: (1) Health Tags (Spire Health), undergarment waistband-adhered physiologic monitors that include a respiratory rate sensor; (2) an app on a smartphone; and (3) a web dashboard for use by respiratory therapists. The physiologic data of 9 patients with COVID out of 1000 patients who were enrolled for monitoring were retrospectively reviewed, and 3 instances were identified where the RPM system had notified clinicians of physiologic deviation due to the viral infection. Results: Physiologic deviations from respective patient baselines occurred during infection onset and, although the infection manifested differently in each case, were identified by the RPM system. In the first case, the patient was symptomatic; in the second case, the patient was presymptomatic; and in the third case, the patient varied from asymptomatic to mildly symptomatic. Conclusions: RPM systems intended for long-term use and that use patient-specific baselines can highlight physiologic changes early in the course of acute disease, such as COVID-19 infection. These cases demonstrate opportunities for earlier diagnosis, treatment, and isolation. This study supports the need for further research into how RPM can be effectively integrated into clinical practice.