Girvan Dempsey returns to the first team after a stomach bug prevented him from starting against Tonga while, in the front-row, Marcus Horan comes in at loose-head, with captain Reggie Corrigan moving across to the unfamiliar tight-head position.
Ulster prop Justin Fitzpatrick, who was replaced by Simon Best during the Tongan game, fails to make the 22-man panel.
The most interesting selection is again in the back-row, where Alan Quinlan comes in at openside ahead of Kieron Dawson of London Irish.
Eric Miller, despite the boot in the face he received against the Tongans, will again start at number eight, while Simon Easterby retains his place at six.
However, there is again no room for Munster flanker David Wallace, with Aidan McCullen instead taking the back-row position on the bench.
The Leinster flanker will make his international debut should he be sprung from the bench, while this will also be the case for Ulster hooker, Paul Shields.
O'Sullivan insisted it was a matter of looking at all of his options ahead of October's World Cup.
"We said that when we came out we would move the backrow around," said the coach.
"It's an area where we have a lot of options. It's just a different combination, we'll see how it works out.
"Up-front, Marcus started in Australia and we're keeping that front row unit together for the last game.
"Anthony Horgan has been showing a pretty good run of form so we want to see how he goes. We need to look down the order in certain situations and I don't think it weakens the team with any of the selections.
"It's just different ways of putting things together."
The conditions have been extremely warm since the Irish side arrived in Apia, with temperatures reaching 35 degrees as the team trained yesterday morning.
However, it is the humidity that is causing most problems for the players and conditions are forecasted to get warmer in the next few days.
"It could be a 22-man effort on Friday," admitted O'Sullivan. "We'll have to manage the pace of the game and if it turns into a seven-a-side tournament, it will be very difficult for us.
"I think we were very fortunate with the weather we got in Tonga, we got a good week of cool weather relatively speaking compared to here. The heat is saturating and it's extremely sapping with the humidity."
As for the Samoans, O'Sullivan is expecting a stiffer challenge than his side received against Tonga.
The game in Nuku'alofa was physically bruising from an Irish point of view, but against the team that are the Pacific Island champions, the coach is expected the bar to be raised.
"The general opinion is that Samoa are a better team than Tonga. They've had a good run of form recently on their Australian tour.
"There're very much a ball in hand side and they play touchline to touchline rugby. If they can dictate the pace of the game in these conditions, it would make things very difficult for us.
"A win on Saturday would be good on a number of fronts. It would be a good win in these conditions, it would be a good win because we've changed the side and there's different combinations.
"It's the last game of a long hard season and, of course, it would be good for morale in the squad.
"Samoa know how to play against the bigger teams and they'd certainly be confident they could take us here."
IRELAND (v Samoa): G Dempsey, J Kelly, M. Mullins, J. Bell, A. Horgan, R. O'Gara, G. Easterby; M. Horan, S. Byrne, R. Corrigan (c), L. Cullen, P. O'Connell, S. Easterby, E. Miller, A. Quinlan.
Subs: P. Shields, E. Byrne, D. O'Callaghan, A. McCullen, B. O'Meara, P. Burke, G. D'arcy.