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Abstract Background Quarantine as a preventive action to reduce people’s exposure to a contagious disease has substantial psychological impact. We aimed to collect information on psychologically distressing experiences of Italians living in quarantine during the COVID-19 pandemic. Methods From 6 to 20 April 2020 participants filled out an online questionnaire. Demographic and physical symptoms data from the prior 14 days of quarantine were collected. Psychological impact of quarantine was assessed by the COVID-19 Peritraumatic Distress Index (CPDI). Results In all, 20,158 participants completed the online survey. Of these, 11,910 (59.1%) were from Lombardy, the region with 37.7% of positive cases identified during the survey period. 30.1% of responders were male. About half (55.9%) of responders were 18–50 years old, 54.3% had a tertiary level of education, 69.5% were workers, 84.1% were living in houses with ≥3 rooms, and 13.7% were living alone. 9.7% had had contact with COVID-19 positive people. Of all responders, 9978 (48.6%) reported a psychological impact, 8897 (43.4%) of whom reported mild or moderate and 1081 (5.2%) severe psychological impact. The multivariate analysis, after adjustments, showed that an increasing CPDI score was associated with gender (female), first-second educational level, being unemployed, living in a ≤2 room house, having had new health problems during the previous 14 days, and not having been out of the house in the previous week. Concerning the type of psychological distress, 2003 responders (9.9%) reported moderate to severe depressive symptoms, 1131 (5.5%) moderate to severe anxiety symptoms, and 802 (3.9%) moderate to severe physical symptoms. A positive correlation was found between responder rate (per 10.000 residents) and positive COVID-19 cases (per 10.000 residents) by region (rs = + 0.83, p = |