The prevalence of infection with VZV in 145 patients with SLE was investigated, with a mean follow-up of 7.6 years; its relationship with different variables, particularly with therapy of the underlying disease, was analyzed. Twenty episodes of VZV infection in 19 patients were diagnosed (13.1%). In no case was the therapeutic regime changed nor was worsening of SLE observed. There was neither dissemination of herpes nor superinfection. An increase in the number of VZV infections was observed in patients with SLE under corticosteroid therapy (p = 0.04) and particularly when drug administration was on a daily basis (p = 0.00006). Cytotoxic agents also favored the infection (p = 0.0014). VZV infection is of a benign nature in SLE and its emergence is favored by immunosuppressive agents. The risk is lower if corticosteroid administration is on alternate days. There is no need to decrease therapy for SLE.