In this pilot study, we explored the immune phenotype of patients with severe obesity and comorbid depressive symptoms compared to non‐depressed patients with obesity and normal‐weight controls. Immune cell subsets were analysed by flow cytometry and depressive symptoms assessed using the Patient Health Questionnaire (PHQ‐9). Cell frequencies were correlated with depressive symptom scores and waist‐to‐hip ratio (WHR). Patients with obesity and comorbid depression showed significantly lower numbers of circulating cytotoxic natural killer cells, dendritic cells and CD8+ effector memory T cells, compared to normal‐weight controls. Regulatory T cells and CD4+ central memory T cells were increased compared to non‐depressed patients with obesity and compared to normal‐weight controls, respectively. Frequencies of cytotoxic natural killer cells and CD4+ central memory T cells significantly correlated with PHQ‐9 scores, but not with WHR. Reduced numbers of dendritic cells were observed in both patient groups with obesity and correlated with PHQ‐9 scores and WHR. These findings provide evidence for an altered immune composition in comorbid obesity and depression, supporting a pathobiological overlap between the two disorders.

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