This study investigated occupational exposure to blood and body fluids among nurses at the emergency department and intensive care units of public hospitals in Addis Ababa city. A cross-sectional study was conducted from June 18, 2021 to September 20, 2021. A simple random sampling method and semi-structured, self-administered questionnaires were used to collect the data, which were analyzed using SPSS version 25. A binary logistic regression model was used to identify factors associated with exposure to blood and body fluids on the AOR with a 95% confidence interval at a P-value of <.05. No patients were involved in this study. Of the total study participants (260), 198 (76%) nurses had been exposed to blood and body fluids in their professional live, and 167 (64%) were exposed to blood and body fluids in the last 12 months. Being male (AOR = 2.88, 95% CI: (1.35, 6.12), lacking access to handwashing facilities (AOR = 5.02, 95% CI: (3.73, 14.51)), not consistently wearing all the required types of personal protective equipment (AOR = 6.21, 95% CI: (2.39, 9.55)), and the lack of the required personal protective equipment (AOR = 5.53, 95% CI: (1.87, 10.38)) were all significant factors that were positively associated with exposure to blood and body fluids. This study showed that a higher proportion of nurses in the emergency department and intensive care unit were exposed to blood and body fluids in the study setting. Most nurses do not consistently wear all the required types of personal protective equipment, putting them at a higher risk of acquiring blood-borne pathogens. The authors recommended that there is a need to implement and strengthen appropriate and consistent use of all required personal protective equipment during any procedure, and patient care to reduce exposure to blood and body fluids. This study provides baseline information for other action-based studies to assess exposure to blood and body fluids among nurses in emergency and intensive care units. This manuscript was prepared based on the strobe checklist guidelines. The study's findings and recommendations might be used for healthcare providers, non-governmental organizations, and policymakers for appropriate planning and interventions to minimize or safeguard nurses' exposure to blood and body fluids.