Palliative care is a medical specialty, which focuses on relieving the suffering and improving the quality of life for patients who are facing life-threatening illnesses and their families. Looking after dying patients is inseparable from our responsibility as physicians. However, dealing with the dying patients is challenging for the majority of physicians. To document the knowledge and attitudes of palliative care among residents from major specialties, Eastern Province, Saudi Arabia. A cross-sectional study was carried out using a self-administered questionnaire to a convenient sample of residents from major specialties from various training centers in Eastern Province, Saudi Arabia, during 2015-2016. A total of 433 residents have been participated in the study. About 46% of the residents showed lack of overall palliative care knowledge, and almost half of them had negative views toward palliative care. Almost 60% of them achieved good score in pain management. The majority of respondents had never received training in palliative medicine (91.7%). It was observed that higher training level has a positive effect on the overall knowledge, including basic concept, pain, and psychiatric symptoms' management. Also, previous exposure to patients who would benefit from palliative care has a direct effect on overall knowledge and attitude scores. The results indicate a low level of knowledge and attitude regarding palliative medicine among sampled residents. Also, it highlights the importance of exposing the residents to palliative medicine field to improve their knowledge and attitude.