We report a 3.5-？ resolution cryo-EM structure of a respiratory supercomplex isolated from Mycobacterium smegmatis. It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate such that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV via a bridging cytochrome subunit. We observe a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for development of treatments for human tuberculosis.