SARS-CoV-2 infection can cause virus-mediated endothelial dysfunction, which in turn may lead to coagulopathy and ischemic microangiopathy. In the critical care population, cutaneous skin manifestations related to vascular compromise due to COVID-19 include livedo and purpura. These lesions can be difficult to differentiate from other dermatologic conditions seen in this population, including skin failure and deep-tissue pressure injuries. In addition, similarities in underlying pathophysiological mechanisms of these skin conditions can cause diagnostic overlap. Skin failure is known to occur in critical care patients owing to disease severity and shunting of blood to vital organs. COVID-19–related ischemic lesions can mimic the clinical course of deep-tissue pressure injury. The viral endothelial dysfunction present in patients with COVID-19 decreases tissue tolerance, which can result in an increased risk of hospital-acquired pressure injury. Extrinsic factors can also complicate diagnosis of cutaneous lesions in patients with COVID-19.