Paul O'Brien may refer to:

• Paul O'Brien (scholar) (1763–1820), Irish language scholar and Catholic priest
• Paul O'Brien (Australian footballer, born 1948), VFL footballer for Fitzroy
• Paul O'Brien (Australian footballer, born 1950), VFL footballer for Carlton
• Paul O'Brien (chemist) (1954–2018), professor of chemistry
• Paul O'Brien (Australian footballer, born 1961), VFL footballer for Essendon and Melbourne
• Paul O'Brien (Scottish footballer) (born 1967), Scottish footballer
• Paul O'Brien (equestrian) (born 1968), New Zealand equestrian
• Paul O'Brien (actor) (born 1978), Australian actor
• Paul O'Brien (rugby league), Australian rugby league footballer of the 1970s