Aims and objectives To clarify both the potential influencing factors and the current status of front-line nurses' work engagement, and thus provide a reference for targeted interventions. Background After coronavirus disease 2019 outbreak, front-line nurses embraced remarkable potential stress and huge workload when caring for coronavirus disease 2019 patients, which may lead to new challenges to work engagement. Design A large sample survey was conducted at the end of February 2020 in a designated hospital treating coronavirus disease 2019 patients in Wuhan, the capital of Hubei Province, in China. t Test, one-way ANOVA, chi-squared test, Pearson's correlation and hierarchical multiple regression were performed among 1,040 nurses using SPSS 24.0. The STROBE checklist was followed for observational studies. Results The final model interpreted 27.3% of the variance, of which each block could explain 11.7%, 10.3% and 7.9% R-2 changes including sociodemographic characteristics, stress and workload, respectively. Work engagement was negatively correlated with stress and workload. The potential influencing factors included sociodemographic characteristics (married, rescue staff, cabin ward), stress (infection control, PPE discomfort) and workload (mental demand, performance, frustration). Conclusions Front-line nurses perceived low stress and workload, but high work engagement, especially in self-dedication. However, infection control, PPE discomfort and frustration were negatively associated with nurses' work engagement, while mental demand and good performance were positively associated with nurses' work engagement. Future interventions focused on decreasing front-line staff's infection risk and enhancing their self-confidence may be recommendable to promote their work engagement.