Graft-vs-host disease (GVHD) after liver transplant is a rare complication with high mortality outcomes. Because of the rarity of occurrence, there is no standardized consensus for treatment. Early recognition of symptoms and a multidisciplinary approach with input from transplant hepatology and hematology is important to determine a treatment plan and improve outcomes. We present a unique case of a 49-year-old woman who developed GVHD during a coronavirus disease 2019 (COVID-19) infection 3 months after receiving a liver transplant. More data are needed to determine whether COVID-19 infection itself correlates with a risk of developing GVHD.