Transcription factor MAFB regulates various homeostatic functions of macrophages. This study explores the role of MAFB in brown adipose tissue (BAT) thermogenesis using macrophage-specific Mafb-deficient (Mafbf/f::LysM-Cre) mice. We find that Mafb deficiency in macrophages reduces thermogenesis, energy expenditure, and sympathetic neuron (SN) density in BAT under cold conditions. This phenotype features a proinflammatory environment that is characterized by macrophage/granulocyte accumulation, increases in interleukin-6 (IL-6) production, and IL-6 trans-signaling, which lead to decreases in nerve growth factor (NGF) expression and reduction in SN density in BAT. We confirm MAFB regulation of IL-6 expression using luciferase readout driven by IL-6 promoter in RAW-264.7 macrophage cell lines. Immunohistochemistry shows clustered organization of NGF-producing cells in BAT, which are primarily TRPV1+ vascular smooth muscle cells, as additionally shown using single-cell RNA sequencing and RT-qPCR of the stromal vascular fraction. Treating Mafbf/f::LysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure. Display omitted •Macrophage MAFB deficiency impairs cold-induced BAT thermogenesis•MAFB loss reduces BAT sympathetic neuron density in the cold•MAFB represses macrophage IL-6 expression via promoter binding•MAFB deficiency in macrophages induces inflammatory environment in BAT Yadav et al. elucidates the role of the transcription factor MAFB in regulating brown adipose tissue (BAT) thermogenesis. They demonstrate that MAFB deficiency in macrophages decreases the neuronal density and thermogenesis of BAT in response to cold, due to an inflammatory state caused by an increase in IL-6, with accumulation of macrophages and granulocytes.