Kaniel Martin, 23, and Avie Howell, 20, both Antiguan nationals, will appear at the Caribbean island's High Court for the start of what is expected to be a lengthy trial.
The Mullanys, from Pontardawe, South Wales, were staying at the five star, £330-a-night Cocos Hotel when intruders broke into their cottage in the early hours of July 27, 2008.
Mrs Mullany, 31, a qualified paediatrician, died instantly from a single gunshot wound to the head.
Her 31-year-old husband, a student physiotherapist, was placed on a life support machine before being flown home to the Morriston Hospital in Swansea, where his wife had worked.
Mr Mullany, a former South Yorkshire Police officer who had also served in the British Army, was pronounced dead a week after the shooting.
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