OBJECTIVES To study the associations between registered nurses' (RNs) perception of the patient safety culture (safety culture) and burnout and sense of coherence, and to compare the burnout and sense of coherence in restructured and not restructured intensive care units (ICUs). DESIGN Cross-sectional study. PARTICIPANTS/SETTING RNs employed at seven ICUs in six hospitals at a Norwegian Hospital Trust. One to four years before the study, three hospitals merged their general and medical ICUs into one general mixed ICU. METHOD The safety culture, burnout and sense of coherence were measured with the questionnaires Hospital Survey on Patient Safety Culture, Bergen Burnout Indicator and Sense of Coherence. Participant characteristics and working in restructured and not restructured ICUs were registered. RESULTS In total, 143/289(49.5%) RNs participated. A positive safety culture was statistically significantly associated with a low score for burnout and a strong sense of coherence. No statistically significant differences were found in burnout and sense of coherence between RNs in the restructured and not restructured ICUs. CONCLUSIONS In this study, a positive safety culture was associated with absence of burnout and high ability to cope with stressful situations. Burnout and sense of coherence were independent of the restructuring process.