Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O2 ) affinity. Calculated oxygen tension at half-saturation (p50 ) was on average (+/-SD) 3.3 (3.13) mmHg lower than the normal p50 value (23.4 vs. 26.7 mmHg; P < 0.0001). Compared to an unmatched historic control of patients with other causes of severe respiratory failure, patients with COVID-19 had a significantly higher Hb-O2 affinity (mean [SD] p50 23.4 [3.13] vs. 24.6 [5.4] mmHg; P < 0.0001). We hypothesise that, due to the long disease process, acclimatisation to hypoxaemia could play a role.