Cytomegalovirus (CMV) infection occurs in 0 to 36% of critically ill patients, mostly between 4 and 12 days after intensive care units (ICUs) admission. Research reported that the ICU stay and mechanical ventilation days of the critically ill patients with CMV infections were longer than those without CMV infections. Studies have suggested that immunocompromised patients such as cancer patients, organ transplant recipients and acquired immunodeficiency syndrome with positive CMV- polymerase chain reaction (PCR) results should be early initiated with anti-CMV therapy to reduce mortality. However, it remains controversial to treat the ICU patients without immunosuppression when the CMV-PCR results were positive. The 74 years old man was brought to the Emergency Room of the hospital due to fever and short of breath. He was intubated for acute respiratory failure and was admitted to the ICU. The CXR showed diffuse miliary lesions over bilateral lung fields. The acid-fast bacilli stain and tuberculosis (TB)-PCR of the sputum both showed positive, so he was mainly given anti-TB therapy. But the patient continued with instability of oxygen saturation, and bilateral pneumonia has not improved. Meanwhile, the CMV-PCR of the sputum and blood showed positive, thus active CMV infection was suspected and ganciclovir infusion was initiated. But after5 days of ganciclovir therapy, the patient still passed away. We recognized a difficult-to-treat case while facing such a severely life-threatening illness, therefore, we remind the possible co-infection of milary tuberculosis and CMV infection and suggest a trial of early diagnosis and early initiation of therapy to control progressive worsening of CMV infection, in order to cure the illness.