Nevin Spence and Eoin O'Malley will form a new centre partnership at this level outside a half-back partnership of Ian Keatley and Isaac Boss.
In the forwards, Damien Varley starts at hooker and beside him experienced Connacht loosehead prop Brett Wilkinson packs down with Stephen Archer, who has recently broken into the Munster matchday squad and been part of the province's Heineken Cup run.
Dan Tuohy wins his third cap at this level and partners Mike McCarthy in the second row. John Muldoon, the most experienced player in the squad at this level with 10 Wolfhounds caps to his credit, forms a back row with captain Chris Henry at openside and Rhys Ruddock starting at number 8 to win his first cap for the Wolfhounds.
O2 Ireland Wolfhounds head coach Eric Elwood is looking forward to the game and the challenge of playing a Saxons team that is packed full of Premiership and European experience.
"The games against the Saxons are always highly competitive affairs as you would expect and results have tended to go with the home side," said Elwood.
"But I think we have a good mix in our side and the key message is that we have to match them on all fronts, especially in the physical stakes, to come away with a win.
"Eoin (O'Malley) and Nevin have done well over the last couple of days as a pairing and I am looking forward to see how both Simon (Zebo) and David Kearney travel on the wings after a good couple of weeks for them with their provinces.
"We have a touch more experience in our pack, which I think will be important for this game and good spine through it with Dan (Tuohy) and Mike (McCarthy) giving us some really good ability across the set piece and in the carrying stakes to compliment a back row that I think can make a good impression.
"I would expect a really good atmosphere for the game and I know the players are looking forward to it."
The match can be seen live on Sky Sports 1/HD1 on Saturday evening, with coverage starting at 4.30pm.
O2 IRELAND WOLFHOUNDS Team & Replacements (v England Saxons, Sandy Park, Exeter, Saturday, January 28, kick-off 5pm):
15 - Gavin Duffy (Galwegians/Connacht)
14 - David Kearney (Lansdowne/Leinster) *
13 - Eoin O'Malley (Old Belvedere/Leinster) *
12 - Nevin Spence (Ballynahinch/Ulster) *
11 - Simon Zebo (Cork Constitution/Munster) *
10 - Ian Keatley (Young Munster/Munster)
9 - Isaac Boss (Terenure College/Leinster)
1 - Brett Wilkinson (Galwegians/Connacht) *
2 - Damien Varley (Garryowen/Munster)
3 - Stephen Archer (Cork Constitution/Munster) *
4 - Dan Tuohy (Ballymena/Ulster)
5 - Mike McCarthy (Buccaneers/Connacht)
6 - John Muldoon (Galwegians/Connacht)
7 - Chris Henry (Ballymena/Ulster) (capt)
8 - Rhys Ruddock (St. Mary's College/Leinster)
16 - Mike Sherry (Garryowen/Munster) *
17 - Ronan Loughney (Galwegians/Connacht) *
18 - Devin Toner (Lansdowne/Leinster)
19 - Kevin McLaughlin (St. Mary's College/Leinster)
20 - Tomas O'Leary (Dolphin/Munster)
21 - Ian Madigan (Blackrock College/Leinster) *
22 - Denis Hurley (Cork Constitution/Munster)
* Denotes uncapped player at full international level