Since the declaration of COVID-19 as a pandemic in 2020, several therapies have been developed to reduce symptoms of COVID-19 infection and prevent progression. Paxlovid is an antiviral that was authorized for emergency use in December 2021 for non-hospitalized symptomatic patients with COVID-19 to prevent progression to severe disease. Relapse of symptoms following a period of improvement after treatment with Paxlovid has been described recently. Data are limited, but the disease course in available case reports is usually mild and requires no additional antiviral treatment. We present the cases of COVID-19 relapse (COVID-19 rebound) in two patients following treatment with Paxlovid.