Aims and objectives To determine the prevalence and to identify the occupational determinants of compassion satisfaction and compassion fatigue among general medical–surgical registered nurses. Background Compassion fatigue and compassion satisfaction are caring concepts that have been explored among nurses in specialised hospital units. However, there is paucity of studies exploring the occupational determinants among general medical–surgical registered nurses. Design Cross‐sectional. Methods From August–November 2017, 121 consecutively selected general medical–surgical registered Nurses from five hospitals completed a four‐part survey packet composed of the participant information sheet, the Professional Quality of Life Version 5, the McCloskey‐Mueller Satisfaction Scale and the Eden Warmth Survey—Employee Questionnaire. Stepwise‐forward multiple linear regression was employed to identify the occupational determinants of compassion fatigue and compassion satisfaction. The STROBE checklist was followed in reporting this study (see Appendix S1). Results The prevalence of moderate to high levels of compassion satisfaction was 90.09% while burnout and secondary stress, the facets of compassion fatigue, had a prevalence of 74.38% and 83.47%, respectively. Among the identified occupational determinants, only job satisfaction and nurse colleague relationship positively influenced compassion satisfaction. In contrary, although higher monthly income positively influenced both dimensions of compassion fatigue, nurse colleague relationship had the strongest negative effect. Conclusion Among the occupational determinants of compassion fatigue and compassion satisfaction, nurse colleague relationship had the strongest influence. This result highlights the importance of positive nurse colleague relationships and paves way for the development and initiation of appropriate strategies. Relevance to clinical practice The findings of this study paves way for the development of institutional policies and individualised programmes geared towards building rapport and communication among registered nurses assigned in general medical–surgical units. Likewise, the high prevalence of compassion fatigue needs further exploration to develop appropriate measures to mitigate its development among general medical–surgical nurses.