Dysfunctional myeloid cells in patients with severe COVID-19 are linked to emergency myelopoiesis, but the exact role of these cells in the disease remains unclear. In this preprint, the authors observed that monocytes from patients with COVID-19 accumulate lipid droplets (LDs). Ex vivo exposure of healthy donor-derived monocytes to SARS-CoV-2 resulted in LD accumulation and upregulation of lipid metabolism targets. Inhibition of LD biogenesis reduced production of pro-inflammatory cytokines, viral replication and death of infected monocytes. Interestingly, the authors also showed that SARS-CoV-2 proteins and double-stranded RNA localize near LDs in infected cells. These results suggest that lipid metabolic reprogramming benefits SARS-CoV-2 infection, and its targeting in myeloid cells may have therapeutic benefit in COVID-19.