We described the etiology and outcomes of CNS infections in a group of Filipino patients with SLE. Risk factors included active SLE in the majority of cases requiring moderate- to high-dose steroids and other immunosuppressants like cyclophosphamide. Although C. neoformans and M. tuberculosis were the most common etiologic agents, it is just as important to search for less common organisms which can produce disease in highly susceptible hosts. A high index of suspicion and early appropriate management are crucial to favorable outcome among these patients.