We try to find the association of cytomegalovirus (CMV) infection and anti-beta2 glycoprotein 1 autoantibodies (anti-beta2 GP1), a key antibody in antiphospholipid syndrome (APS), among systemic lupus erythematosus (SLE) and cerebral vascular accident (CVA) patients. This retrospective study enrolled serum samples obtained from 87 SLE and 97 CVA patients who have been checked for the existence of anti-beta2 GP1. First, the prevalence rate of anti-CMV IgG and IgM in patients with and without anti-beta2 GP1 were compared. Second, the prevalence of anti-CMV IgG and IgM were compared between SLE and CVA patients. Last, this study analyzed the clinical characteristics and disease activity in SLE patients with positive anti-CMV IgM and IgG. No difference existed in the prevalence rate of anti-CMV IgG and IgM between positive or negative anti-beta2 GP1 serum samples in both SLE and CVA patients. However, the prevalence of anti-CMV IgM was significantly higher in the SLE group than in the CVA group. Severity of clinical features and SLEDAI scores were considerably higher in patients with positive anti-CMV IgM than in SLE patients with negative anti-CMV IgM. Very impressively, all IgM-positive SLE samples (9/9) carrying highest levels of anti-CMV IgG, indicated reactivation of the latent CMV infection. Hence, it suggests that CMV reactivation might contribute toward the disease flare in some SLE patients. In future, a prospective and longitudinal study is stongly indicated.