OBJECTIVE: COVID-19 pandemic has been a stressful condition. We explored life changes and health-related consequences of COVID-19 outbreak in Italian healthcare workers in comparison to the general population. METHODS: A total of 593 subjects participated to the online CoRonavIruS Health Impact Survey. Life events and changes, physical health and worries were evaluated referring to 2 weeks prior to the survey. Mood states and daily behaviour were retrospectively evaluated referring to 3 months before COVID-19 (T1) and 2 weeks prior to the survey (T2). Student t test, Mann-Whitney test and multivariate logistic regression analyses were run. RESULTS: Five hundred and twenty-one subjects were analysed (healthcare workers: n = 163, 31.84%; general population: n = 349, 68.16%). Healthcare workers were more likely to report fatigue and have spent more time outside home during the 2 weeks prior to the survey than the general population (χ  = 266.0 , p < 0.001, R  = 0.57). From T1 to T2, healthcare workers had a significant increase in negative mood, worry, restlessness, loneliness and a decrease in happiness, while subjects from the general population had a statistically significant increase in negative mood, worry, attention, concentration difficulties and a decrease in happiness, pleasure related to daily activities, time spent outdoors and alcohol use. CONCLUSION: In the framework of a growing literature on healthcare workers' status during the COVID-19 pandemic, the present study allowed to identify fatigue and loneliness as psychosomatic modifiable variables in need of being monitored and, possibly managed, to ameliorate the health status of healthcare workers.