O'Keeffe's family had been expelled from their property at Glanville during the 1650s, eventually settling at Drumkeene, County Limerick, where he was born.

The family descendants were in Templeglantine until the 1950s' and claimed The Fermoy O'Keeffe Chieftains connection right up to the end.

He received the tonsure at the hands of the Archbishop of Bordeaux on 29 March 1686, having studied at Bruges or Toulouse, or both.

He was listed as an Irish exile in Brittany in 1710, when he was nominated for the rectorship of St. Similien's parish, Nantes.

He stayed there for ten years before returning to Ireland on his appointment as bishop of the Diocese of Limerick by papal brief on 7 March [O.S.