Oxygen therapy has been found to be useful in treating cluster headaches. A double-blind trial compared breathing 100% oxygen with breathing air (nitrogen and oxygen) through a mask for 15 minutes or less during six headache episodes per person. The 100% oxygen significantly reduced the pain of acute cluster attacks in all subjects.⁷ A controlled trial found that during acute episodes of cluster headaches, breathing 100% oxygen through a mask for 15 minutes significantly decreased pain in most of the people with episodic cluster headache and in over half of those with chronic cluster headache.⁸ However, one-fourth of the study participants experienced cluster attacks soon after the treatment was stopped. While oxygen inhalation therapy is now considered a standard treatment,⁹ treatments may need to be repeated, and they have not been shown to help prevent recurrences.

In controlled studies,^{10, 11} a single treatment of hyperbaric oxygen therapy, in which the patient is placed in a chamber with highly concentrated oxygen, has been found to help decrease pain and prevent recurrence of cluster episodes in some patients for several days. Two studies have investigated the use of multiple treatments of hyperbaric oxygen in chronic cluster headache patients. In one small, preliminary trial,¹² ten 70-minute treatments over two weeks brought relief in most of the participants; headaches did not recur for 1 to 31 days after the end of treatment in those who responded. In another preliminary trial, chronic cluster headache patients received 15 hyperbaric oxygen treatment sessions (every other day for 30 minutes each); results showed a gradual decrease in episodes in some patients, which lasted for up to two weeks after treatment ended.¹³