Head coach Stuart Lancaster will rest most of the side beaten by South Africa in the opening Test on Saturday and give the other members of his squad a chance to impress.
Flanker James Haskell, who has not played for England since last year's World Cup, is given an opportunity after not being considered for the first Test in Durban.
The 27-year-old only linked up with the squad last week after completing domestic commitments in New Zealand and it was felt the tour's first midweek game was a more realistic first chance to play.
Scrum-half Danny Care will also start at GWK Park as he bids to resurrect his international career.
The 25-year-old Harlequins back was dropped for the RBS 6 Nations earlier this year after a series of off-field incidents.
Winger David Strettle, who missed the first Test with a calf injury, is given a chance to prove his fitness ahead of the second clash with the Springboks in Johannesburg next weekend.
Prop Alex Corbisiero, whose return after a biceps operation has been delayed by a jarred knee, is not included in Wednesday's team.
Bath's Nick Abendanon, called up to the squad as replacement for the injured Mike Brown, has been named among the substitutes.
Prop Paul Doran Jones, who came off the bench in the 22-17 loss at Kings Park on Saturday, will start at tighthead. Tom Palmer and Lee Dickson, who also had replacements' roles at the weekend, will again be on the bench.
Harlequins' uncapped lock George Robson will captain the side.
Lancaster said: "Every one of the 22 is desperate to play.
"They have trained superbly and their attitude while waiting for their chance has been first class.
"There is a lot of competition for places across the board and Wednesday gives these players a chance to lay down a marker and for the whole squad to build some momentum towards Saturday's Test.
"George (Robson) has had a tremendous season for Harlequins and has made a great contribution to this tour already, both in training and as part of the leadership group, and I know he will captain the team well.
"Only Ugo Monye and Alex Corbisiero will not have had any game time by the end of Wednesday but there will still be three matches to go and their opportunity will come."
England team to face Sourthern Barbarians in tour match at GWK Park, Kimberley, on Wednesday, June 13.
A Goode (Saracens); D Strettle (Saracens), A Allen (Leicester), J Turner-Hall (Harlequins), C Wade (London Wasps); C Hodgson (Saracens), D Care (Harlequins); M Mullan (Worcester), J Gray (Harlequins), P Doran Jones (Northampton), G Kitchener (Leicester), G Robson (Harlequins, capt), J Haskell (Otago Highlanders), C Fearns (Bath), T Waldrom (Leicester).
Replacements: T Youngs (Leicester), R Harden (Gloucester), T Palmer (Stade Francais), J Gibson (London Irish), L Dickson (Northampton), G Lowe (Harlequins), N Abendanon (Bath).
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