Critically ill patients with COVID-19 infection frequently exhibit a hyperinflammatory response and develop organ failures, however the underlying mechanisms are unclear. We investigated the microcirculatory, endothelial and inflammatory responses in critically ill COVID-19 patients and compared them to a group of patients with septic shock in a prospective observational case control study. 30 critically ill patients with COVID-19 were compared to 33 patients with septic shock.Measurements of sublingual microcirculatory flow using Incident Dark Field (IDF) video-microscopy and serial measurements of IL-6 and Syndecan-1 levels were performed. COVID-19 patients had significantly less vasoactive drug requirement and lower plasma lactate than those with septic shock. Microcirculatory flow was significantly worse in septic patients than those with COVID-19 (MFI 2.6 v 2.9 p 0.02, PPV 88 v 97% p < 0.001). IL-6 was higher in patients with septic shock than COVID-19 (1653 v 253 pg/ml, p 0.03). IL-6 levels in COVID 19 patients were not elevated compared to healthy controls except on the day of ICU admission. Syndecan-1 levels were not different between the 2 pathological groups. Compared to patients with undifferentiated septic shock an overt shock state with tissue hypoperfusion does not appear typical of COVID-19 infection. There was no evidence of significant sublingual microcirculatory impairment, widespread endothelial injury or marked inflammatory cytokine release in this group of critically ill COVID-19 patients.