Abstract Introduction: During the last months coronavirus disease 2019 (COVID-19) has spread abruptly to nearly every country, taking on pandemic proportions. The Italian government ordered a nationwide lockdown to hinder the spread of the contagion with unavoidable social isolation and substantial changes in lifestyle habits. Therefore, COVID-19 affected not only physical but also psychological health and well-being. Health care professionals fighting the epidemic represent the most involved category, resulting in more physical and emotional involvement. The aim of this study is to assess the social stress level of health care workers in Italy. Materials and Methods: In this online, totally anonymous survey, 24 multiple-choice questions were broadcast to medical staffs employed in the Italian health care system during COVID-19 pandemic. Data collection was performed from 30th March to 24th April 2020. Descriptive statistics have been applied to describe and summarize our findings and the correlation analyses between categorical variables were performed using Pearson’s Chi-Square. Results: A total of 600 health care professionals completed the questionnaire with a prevalence of young (32.3% between 36 and 45 years old), female (74.0%) oncologists (58.8%). Participants mainly belong to Lombardy (31.3%) and Marche (30.3%), two of the most affected regions, but almost all the Italian regions contributed to the survey. The majority of respondents expressed the fear of being at higher risk of contagion than the general population (83.3%) and the weighty concern of infecting their own families (72.5%). An insufficient supply of personal protective equipment (p = 0.0003) and inadequate training about procedures to follow (p = 0.0092) significantly correlated with these worries. Furthermore, more than two thirds declared a change in family organization and daily life, showing a significant correlation with worry about infecting their own relatives (p < 0.0001). Discussion: This is the first Italian survey on social distress among health care professionals during the COVID-19 pandemic. The unavailability of personal protective equipment, periodic screening procedures, adequate training, and the correct spread of information strongly conditioned health care professionals’ emotional status, family organization, and daily life. With this survey we underlined the social impact that this health emergency has on health care workers, especially on women, who deal with “caring” in the hospital as well as at home, juggling to fulfill multiples roles of professionals, mothers, wives, and caregivers for elderly parents. We wish that institutions could involve themselves concretely to guarantee that health care professionals safely perform their work in a context appropriate to proper professional skills and with the adequate social and psychological support. Reducing workers’ fear of contagion and psychological distress will certainly bring significant positive repercussions for the national health system. Citation Format: Rossana Berardi, Mariangela Torniai, Maria Silvia Cona, Fabiana Cecere, Rita Chiari, Valentina Guarneri, Nicla La Verde, Laura Locati, Domenica Lorusso, Erika Martinelli, Marina Garassino. COVID-19 pandemic in Italy: Social distress and gender imbalance among health care professionals [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-087.