Background: Patients with autoimmune disorders are highly susceptible to infections including cytomegalovirus leading to serious complications ranging from asymptomatic to severe systemic diseases. Case presentation: The first case was a 44-year-old woman with systemic lupus erythematosus referred to the Rheumatology ward due to a necrotizing ulcer on the hand finger and multiple ulcerative lesions on her lips and tongue. She had pancytopenia and positive results for both herpes simplex virus and cytomegalovirus PCR (CMV-PCR); she was treated with Ganciclovir and ultimately recovered. The second case was a 55-year-old man, a known sarcoidosis case, admitted to the hospital due to lower extremities weakness and intraoral ulcers. The lab findings revealed leukopenia and elevated levels of ESR and CRP. Viral markers were all negative except for the CMV-PCR test. EMG-NCV showed subacute axonal motor polyneuropathy in the lower limbs. Due to the high titers of CMV, he was treated with Ganciclovir and the symptoms improved dramatically. Conclusion: CMV infection in rheumatic patients may lead to rare manifestations that can be misdiagnosed as a flare of the underlying disease.