Maintaining therapeutic plasma tacrolimus concentrations is essential for mitigating potential solid organ transplant rejection and preventing toxic adverse side effects. While patients can benefit greatly from tacrolimus therapy, co-administration of drugs such as Paxlovid (nirmatrelvir/ritonavir) place patients at serious risk for drug interactions and harm. Here we present a case of tacrolimus toxicity following Paxlovid administration in a liver transplant patient. Therapeutic drug monitoring was further complicated by a limited upper reportable threshold for tacrolimus testing and highlights the value of validating a higher limit to the clinical reportable range to improve tacrolimus monitoring and meet clinical needs in the setting of drug toxicity.