Hyperbaric oxygen has been used to treat many diseases. However, there are few reports on hyperbaric oxygen treatment for paroxysmal sympathetic hyperactivity at home and abroad, and the clinical experience is very limited. To understand the efficacy of hyperbaric oxygen treatment for paroxysmal sympathetic hyperactivity after brain injury, this retrospective study was conducted in the adult intensive care units of five medical centers in central China. Ninety-two patients with paroxysmal sympathetic hyperactivity syndrome after brain injury were selected from January 2021 to September 2023. Fifty-six patients treated with hyperbaric oxygen were included in the hyperbaric oxygen group, and 36 patients without hyperbaric oxygen treatment were included in the control group. Patients in the hyperbaric oxygen group received 3-5 courses of hyperbaric oxygen treatment, twice daily, once for 70 minutes, 10 days for 1 course of treatment. Compared with before hyperbaric oxygen treatment, the paroxysmal sympathetic hyperactivity symptoms of all patients were significantly relieved after three courses of hyperbaric oxygen treatment. Compared with those in the control group, patients in the hyperbaric oxygen group had higher Glasgow coma scale scores, lower paroxysmal sympathetic hyperactivity syndrome assessment measure scores, and shorter intensive care unit stays. In conclusion, the use of hyperbaric oxygen therapy as an assisted therapy can significantly alleviate the symptoms of patients with paroxysmal sympathetic hyperactivity, thereby providing new ideas for the treatment of paroxysmal sympathetic hyperactivity.