The objective of this study is to identify the clinical differences between infectious meningitis and neuropsychiatric systemic lupus erythematosus (NPSLE) in patients with SLE. Clinical manifestations, laboratory test results, and prognoses of 14 SLE patients complicated with various infectious meningitis, hospitalized in the Affiliated Drum Tower Hospital of Nanjing University Medical School in the past 7 years, were reviewed and compared with those of 34 concomitantly treated NPSLE patients. Our study shows that mortality rate was much higher in SLE patients with infectious meningitis than in NPSLE patients. Compared to NPSLE, those with infectious meningitis had lower SLE Disease Activity Index (SLEDAI), but higher doses of corticosteroids 1 month before the occurrence of CNS symptoms. Headache, high fever, and vomiting were more common in patients with infectious meningitis, accompanied with the elevation of C-reactive protein level. Cerebrospinal fluid (CSF) examination showed increased levels of leukocytes and proteins but decreased glucose level in patients with infectious meningitis. We conclude that for SLE patients exhibiting CNS symptoms, high fever, high intake of corticosteroids, and abnormal CSF are important clues for the coexistence of infectious meningitis, especially tuberculous meningitis.