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BACKGROUND: Symptoms tend to occur in what have been called symptom clusters. Early symptom cluster research was imprecise regarding the causal foundations of the coordinations between specific symptoms, and was silent on whether the relationships between symptoms remained stable over time. This study develops a causal model of the relationships between symptoms in cancer palliative care patients as they approach death, and investigates the changing associations among the symptoms and between those symptoms and well-being. METHODS: Complete symptom assessment scores were obtained for 82 individuals from an existing palliative care database. The data included assessments of pain, anxiety, nausea, shortness of breath, drowsiness, loss of appetite, tiredness, depression and well-being, all collected using the Edmonton Symptom Assessment System (ESAS). Relationships between the symptoms and well-being were investigated using a structural equation model. RESULTS: The model fit acceptably and explained between 26% and 83% of the variation in appetite, tiredness, depression, and well-being. Drowsiness displayed consistent effects on appetite, tiredness and well-being. In contrast, anxiety's effect on well-being shifted importantly, with a direct effect and an indirect effect through tiredness at one month, being replaced by an effect working exclusively through depression at one week. CONCLUSION: Some of the causal forces explaining the variations in, and relationships among, palliative care patients' symptoms changed over the final month of life. This illustrates how investigating the causal foundations of symptom correlation or clustering can provide more detailed understandings that may contribute to improved control of patient comfort, quality of life, and quality of death.