Background: As COVID-19 surged in people experiencing homelessness, leaders at Boston Medical Center (BMC), New England's largest safety-net hospital, developed a program to care for them. Aim: Provide an opportunity for COVID-infected people experiencing homelessness to isolate and receive care until no longer contagious Setting: A decommissioned hospital building. Participants: COVID-infected people experiencing homelessness Program Description: Care was provided by physician volunteers and furloughed staff. Care focused on allowing isolation, managing COVID-19 symptoms, harm-reduction interventions, and addressing problems related to substance use and mental illness. Program evaluation: Among 226 patients who received care, 65% were referred from BMC. Five percent were transferred to the hospital for a complication that appeared COVID-related. There were no deaths, but 7 patients had non-fatal overdoses. Seventy-nine % had at least one diagnosis of mental illness, and 42% reported actively using at least one substance at the time of admission. Thirty % had at least one mental health diagnosis plus active substance use. Discussion: This hospital-based COVID Recuperation Unit was rapidly deployed, provided safe isolation for 226 patients over 8 weeks, treated frequent SUD and mental illness, and helped prevent the hospital's acute-care bed capacity from being overwhelmed during the peak of the COVID-19 epidemic.