M1 macrophages are pro-inflammatory, whereas M2 macrophages are involved in tissue repair. Here, Spence et al. study the role of suppressor of cytokine signalling 2 (SOCS2) and SOCS3 in macrophage polarization. The phenotypes of Socs2−/− or Socs3−/− macrophages were analysed in the absence or presence of polarizing stimuli, and their function was tested in a mouse model of sepsis. Socs2−/− macrophages were biased towards the M1 subset, whereas Socs3−/− macrophages had a stable M2 profile. Moreover, compared with controls, Socs2−/− macrophages had higher levels of phosphorylated STAT1 (signal transducer and activator of transcription 1) following stimulation with interferon-γ, and Socs3−/− macrophages had higher levels of active STAT6 in response to interleukin-4. As the blockade of these cytokines partially reversed the polarization bias of Socs2−/− and Socs3−/− macrophages, SOCS2 and SOCS3 may control macrophage polarization by regulating cytokine–STAT signalling.