Background and purpose: Data concerning the characteristics and duration of the critical manifestations, treatment response, and long-term outcomes of severe anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients compared to those of non-severe patients are limited. This observational study was performed to explore the clinical characteristics and long-term outcomes of severe anti-NMDAR encephalitis patients. Methods: According to their characteristics on admission to the neurology intensive care unit, patients with anti-NMDAR encephalitis were divided into a severe group and a non-severe group. The demographics, clinical manifestations, main accessory examinations, immunotherapy, and outcomes of patients were recorded. Statistical analyses were employed to examine the differences in each observed indicator between the severe and non-severe groups. Results: This study enrolled 111 patients with anti-NMDAR encephalitis, including 59 males and 52 females with a mean age of 27.7 +/- 13.7 years; 39 (35.1%) patients were in the severe group, and 72 (64.9%) patients were in the non-severe group. Compared to the non-severe group, the severe group exhibited a higher proportion of epilepsy, involuntary movement, disturbance of consciousness, autonomic dysfunction, and central hypoventilation. The cerebrospinal fluid (CSF) of all patients was positive for the NMDAR antibody, but only 57 patients (51.4%) tested positive for the NMDAR antibody in the blood. The proportion of patients with a strong positive NMDAR antibody titer in the severe group (48.7%) was higher than that in the non-severe group (29.2%). The proportion of patients receiving intravenous gamma immunoglobulin in the severe group was higher than that in the non-severe group (P = 0.003), and only patients in the severe group received plasma exchange, intravenous rituximab, and cyclophosphamide treatment. No significant difference was observed in the prognosis between the severe group and the non-severe group after 6 months and during long-term follow-up. Conclusion: Most severe anti-NMDAR encephalitis patients will eventually achieve good long-term prognoses after receiving early, positive and unremitting combined immunotherapy and life support.