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Sir Donough O'Brien, 1st Baronet (1642 – 17 November 1717) was an Irish politician and baronet.
He was the son of Connor O'Brien and his wife Maire Rua McMahon. In 1692, O'Brien entered the Irish House of Commons, sitting for Clare until 1714.
He married firstly Lucia Hamilton, daughter of Sir George Hamilton and had two sons, Brian O'Brien and Lucius O'Brien. Lucius was the father of Sir Edward O'Brien, 2nd Baronet.