Lipedema is an adipose tissue disorder characterized by abnormal development of fatty tissue in the lower body parts of patients. The adipose tissue microenvironment plays an essential role in the metabolic and physiological homeostasis of fat development and distribution. However, the microenvironment and cellular composition of lipedema adipose tissue have not been characterized. This study used single-cell RNA sequencing to analyze adipose tissue cell populations in lipedema. We thus identified differences in the adipose tissue stromal vascular fraction of body mass index-matched lipedema and non-lipedema control (obese) patients. Clustering of immune and non-immune cellular components of adipose tissue allowed the identification of multiple immune cells (macrophages, B cells, monocytes, dendritic cells, and NK cells) and structural cells (adipose-derived progenitor stem cells, preadipocytes, endothelial cells, fibroblasts, and smooth muscle cells). By comparing lipedema and non-lipedema adipose tissue, we identified lipedema-specific differences in the abundance of various cell types, the presence of key cellular markers, and patterns of gene expression. Data integration and comparative analysis revealed highly differentially expressed genes in lipedema versus non-lipedema, and the involvement of metabolic pathways, cytokine & chemokine signaling, insulin signaling, adhesion, adipogenesis, and lipid metabolism pathways in lipedema. Our adipose tissue transcriptome atlas provides an important resource for studying the biology of lipedema and identifying potential diagnostic or therapeutic targets.