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Mark O'Brien may refer to:
- Mark O'Brien (actor) (born 1984), Canadian actor
- Mark O'Brien (cyclist) (born 1987), Australian cyclist
- Mark O'Brien (footballer, born 1984), Irish footballer, plays for Shelbourne F.C.
- Mark O'Brien (footballer, born 1992), Irish footballer, plays for Newport County A.F.C.
- Mark O'Brien (poet) (1949–1999), American poet and advocate for the disabled
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