Paxlovid TM (nirmaltrelvir/ritonavir) received emergency use authorization from the Food and Drug Administration (FDA) in December 2021 to treat coronavirus disease 2019 . Given the actions of Paxlovid on cytochrome P450-3A4 (CYP3A4) enzymes, it is imperative to check for potential drug-drug interactions before prescribing. We describe a case in which the common emergency department presentation of generalized weakness was found to be caused by interactions between Paxlovid and a patient's home medications resulting in tacrolimus toxicity.