Background: Patients with palliative-stage cancer often suffer from a variety of debilitating symptoms which have been shown to appear in clusters. It is suggested that cytokines cause many such symptoms, and elevated cytokine production has been shown to correlate with symptoms. However, symptom clusters have not been thoroughly analyzed in relation to cytokine clusters. The aim of the present study was to identify symptom clusters and cytokine clusters in Swedish cancer patients, and to investigate correlations between the identified symptom clusters and cytokine clusters. Methods: The EORTC Quality of Life Questionnaire Core 15 Palliative Care questionnaire was completed by 110 cancer patients, with blood samples taken at two time points four weeks apart. Meso scale discovery (MSD) assays were used to analyze 23 cytokines. Statistical analysis was performed using principal component analysis (PCA) of symptoms and cytokines, followed by correlation analysis of the obtained clusters. Results: Three symptom clusters were identified: (I) pain-sleep disorder, (II) gastro-intestinal-fatigue, (III) physical functioning. The cytokines were divided into three clusters that can be characterized as (I) pro-tumorigenic, (II) cell-mediated immune response and (III) proinflammatory. At the second time point, a fourth cytokine cluster was isolated (IV) immunostimulation. Correlations were found at both time points between the proinflammatory cytokine cluster and the physical functioning symptom cluster, and at the week four time point between the proinflammatory cytokine cluster and the gastro-intestinal-fatigue symptom cluster. Conclusions: We show a correlation between symptom clusters and the proinflammatory cytokine cluster. Proinflammatory cytokines are known to cause symptoms that resemble palliative cancer symptoms. Increased knowledge of biochemical processes and their effect on patients’ wellbeing may give clues for counteracting symptoms that affect quality of life (QOL) in palliative cancer care. © Annals of Palliative Medicine. All rights reserved.