Chronic granulomatous disease (GCD) is characterized by severe infections, notably with Burkholderia cepacia complex (BCC). GCD is rarely complicated by lymphohistiocytic activation syndromes, most often secondary to bacterial or viral infections, in particular human herpes virus 6 (HHV-6). We describe the case of a 10-month-old boy who suffered from multiple organ failure due to a BCC infection and a lymphohistiocytic activation syndrome, leading to diagnosis of GCD. The initial search for HHV-6 was positive and the infection was treated, but the progression and viral sample analysis led to the chromosomal integration of the HHV-6 genome. The child's clinical condition was normal after bone marrow transplantation. This case describes a rare association between GCD and lymphohistiocytic activation syndrome and raises questions about the role played by chromosomal integration of the HHV-6 genome.