Background: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the importance of implementing strategic management that prioritizes the safety of frontline nurse professionals. In this sense, this research was aimed at identifying factors associated with the illness of nursing professionals caused by COVID-19 according to socio-demographic, clinical, and labor variables. Methods: A cross-sectional study was conducted in three Brazilian university hospitals with 859 nursing professionals, which include nurses, technicians, and nursing assistants, between November 2020 and February 2021. We present data using absolute and relative frequency. We used Chi-square test for hypothesis testing and multiple logistic regression for predictive analysis and chances of occurrence. Results: The rate of nursing professionals affected by COVID-19 was 41.8%, and the factors associated with contamination were the number of people in the same household with COVID-19 and obesity. Being a nurse was a protective factor when the entire nursing team was considered. The model is significant, and its variables represent 56.61% of the occurrence of COVID-19 in nursing professionals. Conclusion Obesity and living in the same household as other people affected by COVID-19 increases the risk of contamination by this new coronavirus.