Introduction The preparedness of nurses in relation to providing palliative care is not always adequate, indeed, it is sometimes unsatisfactory; this may be caused by lack of knowledge and limited experience in end-of-life care (EOLC). Thus, this study purposed to assess the levels of registered nurses' knowledge about EOLC, examine the relationships between EOLC knowledge and some demographic variables, and explore predictors of EOLC knowledge. Methods A cross-sectional design survey was conducted with Jordanian registered nurses in critical care units (N = 175) in different heath sectors in Jordan. The End-of Life Professional Caregiver Survey (EPCS) was used. Results Findings showed that nurses had moderate/quite a lot of knowledge (M (SD) = 2.58 (.48)) about EOLC. The cultural and ethical values was the highest subscale of knowledge about EOLC (M (SD) = 2.74 (.52)), while effective care delivery subscale was the lowest one ( (M (SD) = 2.33 (.66). Knowledge about EOLC was correlated with age ( r = .145, P < .05), work experience ( r = .173, P < .05), and training course in palliative or EOLC (r = .217, P < .01). The main predictor of EPCS was training courses in palliative or EOLC (B = .190, P < .05). Conclusion The nurses need to enhance their knowledge about EOLC and correlating factors should be taken into consideration when developing any intervention program. Nurses need palliative care training courses; also more attention is required in palliative care education particularly in clinical skills in effective care delivery.