AbstractLack of established knowledge and treatment strategies, and change in work environment, may altogether critically affect the mental health and functioning of physicians treating COVID-19 patients. Thus, we examined whether treating COVID-19 patients affect the physicians’ mental health differently compared with physicians treating non-COVID-19 patients. In this cohort study, an association was blindly computed between physiologically measured anxiety and attention vigilance (collected from 1 May 2014 to 31 May 31 2016) and self-reports of anxiety, mental health aspects, and sleep quality (collected from 20 April to 30 June 2020, and analyzed from 1 July to 1 September 2020), of 91 physicians treating COVID-19 or non-COVID-19 patients. As a priori hypothesized, physicians treating COVID-19 patients showed a relative elevation in both physiological measures of anxiety (95% CI: 2317.69–2453.44 versus 1982.32–2068.46; P < 0.001) and attention vigilance (95% CI: 29.85–34.97 versus 22.84–26.61; P < 0.001), compared with their colleagues treating non-COVID-19 patients. At least 3 months into the pandemic, physicians treating COVID-19 patients reported high anxiety and low quality of sleep. Machine learning showed clustering to the COVID-19 and non-COVID-19 subgroups with a high correlation mainly between physiological and self-reported anxiety, and between physiologically measured anxiety and sleep duration. To conclude, the pattern of attention vigilance, heightened anxiety, and reduced sleep quality findings point the need for mental intervention aimed at those physicians susceptible to develop post-traumatic stress symptoms, owing to the consequences of fighting at the forefront of the COVID-19 pandemic.