England's South African born prop Matt Stevens has been ruled out of the five match, three Test tour of South Africa and Gloucester prop Rupert Harden has been called into the England squad.
Twenty-nine-year-old Stevens returned to rugby last year after serving a two-year suspension for testing positive for cocaine but suffered a shoulder rotator cuff injury during Sunday's Killik Cup victory against the Barbarians.
England are facing concerns over the fitness of fly-half Toby Flood and the availability of Leicester Tigers centre Manu Tuilagi.
Tuilagi could miss the entire tour to South Africa after being cited for a "tip" tackle on Danny Care during last weekend's Premiership play-off final against Harlequins at Twickenham.
With Elite Player Squad members Henry Thomas and David Wilson injured, 26-year-old Harden will join England training immediately ahead of flying to South African Wednesday.
England Head Coach Stuart Lancaster said: "Firstly, it's really tough on Matt but he has been assessed by the medics and he wouldn't be able to train or play for some time."
"We wish him all the best but it's a great opportunity for Rupert, who has been the first choice tight head for Gloucester this season and also involved in the Saxons during the Six Nations."