Patients with SLE carry an increased risk of infection that account for 11-23% of all hospitalized patients and 50% of all SLE patients develop major infections during the course of their disease. Globally Herpes Zoster has been reported as the most frequent viral infection in SLE patients. We determined the clinical spectrum, disease sequelae and the risk factors associated with the development of Herpes Zoster in patients with SLE and their outcomes. Retrospective case control study of Herpes Zoster infections was done in SLE patients between 1982 and 2006. Cases were matched 1:2 to controls for age, race, sex and duration of follow up. Clinical features of the cases from the time of lupus diagnosis to the time of Zoster were compared to their respective controls over similar time periods. Thirty two SLE cases were compared to sixty four controls. Cases were more likely to have received cyclophosphamide (P = .0223) and intravenous methylprednisolone pulse therapy (P = .0026), MMF (P < .02), had leucopenia (P = .0407) and hemolytic anemia (P = .0344). More cases than controls had lupus nephritis, cerebritis, thrombocytopenia but the differences did not reach statistical significance. The mean oral prednisolone dose and proportion of patients receiving immunosuppressives including pulse methylprednisolone therapy, IV Cyclophosphamide and mycophenolate was significantly higher in patients with active SLE compared to patients with SLE in remission at the time of Herpes Zoster (P < .05). Disseminated Zoster developed in patients with active SLE (7/9) compared to patients with SLE in remission (0/23). None of the patients had postherpetic neuralgia or bacterial super infection. Immunosuppressive medications were discontinued at the time of diagnosis of Zoster in 19 of 32 patients and all patients received antiviral medications.There were no permanent neurologic deficits or deaths. We conclude that Herpes Zoster infections occur at increased frequency among patients with SLE and carry significant morbidity. Immunosuppressive therapy and severe manifestations of lupus may be risk factors for the development of Herpes Zoster although not necessarily at the time of disease flare or immunosuppressive therapy. Our study suggests that although Herpes Zoster occurs frequently in patients with SLE, it has a relatively benign course.