Patients with and without COVID-19 have a wide range of physiological responses to hypoxaemia. COVID-19 patients are not more physiologically "happy" in response to hypoxia, and have greater respiratory rates for any given SpO2/FiO2 ratio. In COVID-19, decreasing physiological "happiness" in response to hypoxaemia is related with worse results. From bedside observations, the ROX index may be a straightforward tool for distinguishing patients at risk of bad outcomes in COVID-19.