Paxlovid (nirmatrevir/ritonavir) is a 2 drug regimen taken together twice daily for 5 days was authorized for emergency use for nonhospitalized patients who are at risk for the progression of coronavirus disease (COVID-19). However, recurrence of symptoms 2–8 days after completing the treatment course has been recently recognized. In some cases patients tested negative on a direct SARS-CoV-2 viral test and then tested positive again (rebound COVID-19). The disease is mild and requires no additional antiviral treatment. Data are limited based on anecdotal case reports and few studies. According to the available data it is unclear if rebound symptoms are due to the drug treatment, drug resistance, re-infection or impaired immunity.