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The serological prevalence of Epstein-Barr virus (EBV) among young adults exceeds 90% worldwide. Even though EBV primary infection is usually benign, severe complications can occur in adolescents and young adults and so the disease must be promptly diagnosed. The development of an oropharyngeal abscess leading to a descending necrotizing mediastinitis (DNM) is exceptional and potentially lethal, so early diagnosis with a CT scan, appropriate antibiotics and surgery are essential.  The authors present a case where DNM was associated with reactive hemophagocytic syndrome as a result of infectious mononucleosis, as well as a review of similar cases in the English literature.