He was later elected to the House of Commons of the United Kingdom of Great Britain and Ireland, as a Member of Parliament (MP) in the Irish Parliamentary Party.

In September 1849, he participated an attack, organised by James Fintan Lalor, on Cappoquin police barracks and evaded arrest, [2] fleeing to Wales on one of his father's merchant ships for a number of months.

However, a year later he left for Paris, with his friend John O'Leary, where he continued his studies, attending the École de Médecine.

[4] Upon his arrival to New Orleans, O'Brien was persuaded to participate in William Walker's Filibuster War in Nicaragua.

Next, O'Brien worked as a replacement lecturer for Richard D'Alton Williams at the Jesuit College in Baton Rouge, Louisiana.

The idea was that if O'Donovan Rossa, who was already known to the public as a Fenian, was elected to as an MP, this would be highly embarrassing for the British state.

Parnell had previously requested that the Irish National League withdraw the nomination of Pat Nally as their South Mayo candidate in an upcoming election.

Nally had been previously arrested and convicted of participating in the "Crossmolina Riot", which had received national press coverage across the United Kingdom.

The Mayo branch of the Irish National League wanted to make Nally an MP in protest but Parnell did not like the idea.