From 1725 to 1727, O'Brien sat as a Member of the Irish House of Commons for Charleville.[1] In 1727, he was elected to the Irish House of Commons for Youghal. He held this seat until his retirement in 1760.[1] While serving in Parliament, O'Brien and his family lived in Drogheda, where he held the position of Collector of Customs for the Port of Drogheda. He retired to his brother's estate at Rostellan, County Cork. During his residency there, O'Brien served as Collector of Customs for the Port of Cork until 1767. He died at Rostellan Estate in 1771.[citation needed]
Children of James O'Brien and Mary Jephson:[citation needed]
Anne O'Brien (1724 – 19 January 1745) married the Most Reverend Michael Cox, Archbishop of Cashel and died in childbirth with her only son nine months after the wedding.
Henrietta O'Brien (1737 – 17 November 1797) Married first to Terence O'Loughlin. Married second to Sir William Vigors Burdett, 2nd Baronet Burdett of Dunmore, son of Sir Thomas Burdett, 1st Baronet and Martha Vigors. They had one son.