Mendelian Susceptibility to Mycobacterial Disease describes a spectrum of inherited defects, of which complete deficiency of the interleukin-12 receptor β subunit 1 (IL-12Rβ1) is the most common cause. This condition results in a predisposition to severe disease caused by mycobacteria. We report a case of disseminated multidrug-resistant tuberculosis with extensive central nervous system affection with SARS-CoV-2 co-infection, in a 4-year-old child with IL-12Rβ1 complete deficiency.