Abstract Background The COVID-19 pandemic has affected healthcare institutions and workers, exposing them to unfamiliar and hazardous conditions, increased workloads, and changing directives. This has led to work-related stress, resulting in burnout, depression, anxiety disorders, and other health issues among healthcare workers. Methods This cross-sectional study utilized an anonymous questionnaire with closed-ended questions. To assess stress levels among healthcare workers, a Likert-type scale was used. Over 6.000 healthcare workers completed the questionnaire in 2022. The relationship between the dependent variable (perceived stress level) and predictors was modelled using generalized ordinal univariate and multivariate logistic regression. Results Almost a third (30.7%) of respondents felt a very high amount of tension, stress, or pressure while performing their jobs under the conditions of the COVID-19 epidemic, while 422 (6.8%) did not feel tension, stress, or pressure at all. In the multivariate logistic regression model, statistically significant predictors of higher levels of perceived stress in the conditions of the COVID-19 epidemic include female sex (OR = 0,80), older age (OR = 1.19), being in a managerial position (OR = 1.32), lower satisfaction with available work time (OR = 0.82), patient relations (OR = 0.81), financial compensation (OR = 0.83), and cooperation with colleagues (OR = 0.93). Conclusions Through the identification of potential stress predictors, valuable insights are gained to aid policymakers in the planning and enhancement of healthcare personnel’s work during pandemics, as well as in situations characterized by heightened stress levels. Key messages • These findings emphasize supporting healthcare workers during the pandemic. • Strategies for reducing stress should be directed towards healthcare professionals who experience higher stress levels.