Nick Evans is set to make his first appearance since February on Friday night after being named on the bench for Harlequins' European Challenge Cup semifinal against Grenoble.
Evans had been expected to be out for 12 weeks with a broken leg, suffered against Gloucester, and his return comes almost a month ahead of schedule.
The Kiwi fly-half is joined in the match-day 23 by James Horwill, Adam Jones, Joe Marler, George Lowe and Luke Wallace, all of whom return to the starting 15 having missed last Saturday's 22-12 defeat to Saracens at Wembley.
"Nick has fought back fit a couple of weeks ahead of schedule but that's only what we've come to expect of him," said O'Shea, who has named Ben Botica as the starting fly-half.
"He's proved his tenacity and drive so many times with us over the years, that when we knew the extent of his injury we all also knew that he would do everything he could to be back out on the field as soon as possible.
"It's a great boost to have him back and something that will give everyone a natural lift -- but at the same time Ben Botica has been playing excellently and fully deserves his place.
"We feel it's a strong line-up and a strong place for us to be at the moment, so hopefully we can go out there on Friday night and bring that to bear against what is clearly a powerful Grenoble side."
Marler returns following his two-match suspension for the "Gypsy boy" slur against Wales' tighthead Samson Lee during the Six Nations.
Harlequins squad (to play Grenoble):
Brown, Yarde, Lowe, Roberts, Visser, Botica, Care (captain); Marler, Gray, Jones, Horwill, Twomey, Robshaw, Wallace, Easter
Replacements: Ward, Lambert, Sinckler, Matthews, Clifford, Dickson, Evans, Chisholm
The Press Association contributed to this report.