Coronavirus disease 2019 (COVID-19) is associated with a high incidence of thromboembolic events, both venous and arterial. There are currently no specific clinical or laboratory markers to guide antithrombotic therapy for COVID-19 patients. Immature platelets represent a population of hyper-reactive platelets associated with arterial thrombotic events. This prospective study compared consecutive severe COVID-19 patients (n = 53, median age = 73 years) versus patients with sepsis from another origin (n = 41, median age = 69 years). Total platelet counts, immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points. IPC levels three days after admission were significantly higher in the COVID-19 group compared to the sepsis group (13.4 × 10