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O'Brien could refer to:
- Miles O'Brien, transporter chief aboard the USS Enterprise-D, and Chief of Operations aboard Deep Space 9
- Keiko O'Brien, biologist and wife to Miles O'Brien
- Molly O'Brien, first child of Miles and Keiko O'Brien
- Kirayoshi O'Brien, second child of Miles and Keiko O'Brien
- Michael O'Brien, father of Miles O'Brien
- Miranda O'Brien, an alternate timeline descendant of Miles O'Brien
- Sean Aloysius O'Brien, labor union leader in the 20th century, and ancestor to Miles O'Brien
- O'Brien family, the family unit that Miles and Keiko belong to
- O'Brien, a character in the Dixon Hill stories
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