Several months after the sudden emergence of SARS-CoV-2 and COVID-19, the understanding of the appropriate host immune response to a virus totally unknown of human immune surveillance is still of major importance. By international definition, COVID-19 falls in the scope of septic syndromes (organ dysfunction due to dysregulated host response to an infection) in which immunosuppression is a significant driver of mortality. Sepsis-induced immunosuppression is mostly defined and monitored by the measurement of decreased expression of HLA-DR molecules on circulating monocytes (mHLA-DR). In this interim review, we summarize the first mHLA-DR results in COVID-19 patients. In critically ill patients, results homogenously indicate a decreased mHLA-DR expression, which, along with profound lymphopenia and other functional alterations, is indicative of a status of immunosuppression. © 2020 International Society for Advancement of Cytometry. © 2020 International Society for Advancement of Cytometry.