O'Brien is an unincorporated community in Suwannee County, Florida, United States, located along U.S. Route 129 at the intersection of County Road 349, north of Branford.

O'Brien has a post office with ZIP code 32071.

[2] O’Brien was established in 1880, and was originally known as OBrien Station as it was on the railroad route between Live Oak and Branford.

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