Background: Stress in nurses refers to the reactions nurses experience when faced with work demands that exceed their knowledge, skills, or ability to cope. Nursing, as a profession, is particularly susceptible to work-related stress. Methods: A cross-sectional study was conducted among 405 randomly selected nurses working in Hadiya Zone public hospitals from March 1 to 30, 2023. Data were collected using a pre-tested self-administered questionnaire. The data were entered using Epi-data version 3.1, and analysed using SPSS version 20.0. Multivariable logistic regression analysis was performed to identify factors associated with the level of work stress. Variables with a p-value <0.05 were considered statistically significant. Results: In this study, 56% (95% CI 50.9-61.2) of the participants reported being stressed in their work. Several factors were found to be associated with work stress, including being female (AOR=1.94, 95% CI 1.19-3.16), rotating shifts (AOR=2.06, 95% CI 1.31-3.25), working in the intensive care unit (AOR=3.42, 95% CI 1.20-9.73), and having post-basic training (AOR=0.55, 95% CI 0.34-0.92). Conclusion: The study revealed a high level of work stress among nurses in the study area. The zonal health unit takes measures to address work stress by providing job orientation during the hiring process, rotation, and on-the-job training to help nurses cope with and manage stressful events. Stress in public hospitals and among nurses is an important issue that needs urgent attention.