Cytomegalovirus (CMV) infection is asymptomatic in the majority of immunocompetent patients. However, it can cause severe presentations, particularly in patients who are immunocompromised. We are reporting a rare association between respiratory failure secondary to cavitary pneumonia and a large pericardial effusion due to CMV infection in a patient with human immunodeficiency virus. The patient presented with hypoxic respiratory failure and a large pericardial effusion at risk of tamponade. After extensive investigation, the sole pathogen identified in the patient's bronchoalveolar lavage and pericardial fluid was CMV.