CMV is a highly prevalent virus in the adult population (60–100%) and in healthy adults is usually asymptomatic or causes only a mild mononucleosis-like syndrome. We, here, report on 2 CF patients, who contracted a CMV primoinfection, which caused significant morbidity. Patient 1 was a 41 year-old CMV-negative man who suffered from severe, but only slowly progressive, CF lung disease and ABPA. In 08/2013, he presented with an acute pulmonary exacerbation and fever, which was unusual, as well as asthenia. A CMV primoinfection was diagnosed, but left untreated. However, he went on to deteriorate acutely, had to be intubated, presented massive hemoptysis, had to be assisted with ECMO and had to undergo urgent bilateral lung transplantation (LTx). Patient 2 was a 30 year-old CMV-negative man, who also suffered from severe CF lung disease and ABPA. In 05/2014, he developed prolonged fever and profound asthenia in the context of CMV infection. The deterioration was such that he had to be waitlisted for LTx. He was treated with iv ganciclovir followed by oral valganciclovir. Both patients had received courses of oral corticosteroids for ABPA in the past. Most notably, both had become fathers within 12–24 months before infection and were, thus, exposed to a small child at home. The children were evidently not tested for CMV infection because of ethical concerns, but were believed to be a plausible source of infection in both fathers. CMV primoinfection may cause significant morbidity in sicker adult CF patients. The index of suspicion should be high in CMV-negative patients exposed to small children. The appropriate management is unknown at the present time.