Since its emergence, in December 2019, COVID-19 has resulted in more than 12 million people infected and has killed more than 570000. Hypoxemia HP has been identified as one of the main clinical manifestations of this disease MESHD, especially in severe cases. We have previously reported that in critically ill COVID-19 patients there is a shift towards an immature myeloid profile in peripheral blood SERO cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, which, together with mature monocytes and segmented neutrophils, comprise the vast majority of blood SERO cells in these patients. Such an immature myeloid profile may be the result of a physiological response known as emergency MESHD myelopoiesis. In the present study, we performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia MESHD-inducible factor1α (HIF1α) mRNA and its transcriptionally regulated genes. HIF1α is a master transcription factor involved in the cellular response to hypoxia MESHD. We herein report that these cellular subsets express high levels of HIF1α mRNA and several of their transcriptional targets, including those related to inflammation MESHD, such as CXCL8, CXCR1, CXCR2, and CXCR4; those potentially involved in virus sensing, such as TLR2 and TLR4; and those related to metabolism, such as SLC2A3, PFKFB3, PGK1, GAPDH and SOD2. The up-regulation and participation of HIF1α in relevant events such as inflammation MESHD, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.