Background <p>Severe combined immunodeficiency(SCID) combined with Bacillus Calmette-Guérin(BCG) disease(BCG-osis) is a rare but life-threatening complication in pediatric patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early recognition and intervention are essential to prevent severe complications.</p> Case presentation <p>We have described two pediatric cases of SCID combined with BCG-osis in which the patients received salvage therapy with allo-HSCT. Data were collected from two male infants who underwent allo-HSCT for SCID with BCG-osis at Wuhan Children’s Hospital between January 2017 and December 2022. The data of the two patients were retrospectively collected and analyzed to summarize their clinical characteristics, treatment, and prognosis. Patient 1 presented with SCID combined with disseminated BCG-osis and underwent HSCT after only 30 days of anti-tuberculosis therapy. The tuberculosis infection recurred at 83 days after transplantation, and the patient eventually died of multi-organ failure and disseminated intravascular coagulation. Patient 2 presented with SCID combined with disseminated BCG-osis after HSCT. The patient responded well to antituberculosis drugs and successfully completed a year and a half of anti-tuberculosis treatment. On day 591 post-transplant, the anti-tuberculosis regimen was discontinued in this patient.</p> Conclusions <p>Patients with SCID have severe defects in cellular and humoral immunity. Genetic screening at birth would help identify such patients, and the BCG vaccination should be delayed in such cases. The sole curative option for SCID is HSCT, which can achieve immune reconstitution when performed early on and can improve the survival rate.</p>