Sean O'Brien may refer to:
- Seán O'Brien (Gaelic footballer), Gaelic footballer with Nemo Rangers
- Sean O'Brien (rugby player) (born 1987), Irish rugby union player
- Sean O'Brien (writer) (born 1952), British writer
- Sean O'Brien (musician), bassist and original member of Boston rock band Come
- Sean O'Brien (scientist), co-discoverer of buckminsterfullerene
- Seán O'Brien (hurler), Irish hurler
- Sean O'Brien (ice hockey) (born 1972), American former ice hockey left winger
- Sean O'Brien (Ohio politician), Democratic member of the Ohio House of Representatives