Autosplenectomy in systemic lupus erythematosus (SLE) is associated with a high mortality rate due to Streptococcus pneumoniae sepsis. We describe 2 patients who developed autosplenectomy in the setting of an acute SLE exacerbation. Followup of both patients 12 and 5.5 years after the initial diagnosis of autosplenectomy revealed persistent absence of the spleen. Pneumococcal vaccine was given to both patients. In contrast with reports describing life threatening infections in 46.7% of asplenic patients with SLE, none developed during prolonged followup of our patients. Our data and review of 13 other patients with SLE with autosplenectomy suggest that the 23-valent pneumococcal vaccine should be given promptly to patients with SLE when a diagnosis of autosplenectomy is established.