Martin O'Neill's squad fly out to the United States for friendlies against Costa Rica in Philadelphia and Portugal in New Jersey, and he will have the chance to look at some different options at the back.
On top of the key defensive trio, who had been expected to stay at home, Wolves utility player Stephen Ward will also miss the Costa Rica game, but he could arrive in time to play Portugal on June 10.
O'Neill oversaw his final training session before the flight in Malahide on Tuesday with a number of other players absent.
Aston Villa defender Ciaran Clark suffered a minor knee injury before the 0-0 draw with Italy on Friday and he is still receiving treatment with his club.
Stoke forward Jon Walters is suffering with a stomach bug, and midfielders Wes Hoolahan and David Meyler were given the day off to try and recover from knocks they suffered against the Italians.
They are following recovery programmes but are still expected to travel with the squad on Wednesday, while Anthony Pilkington did routine post game gym work instead of training according to the Football Association of Ireland.