For Ulster's return to league action, Cave will be partnered in midfield by Jared Payne who switches from full-back to outside centre.
In the back-three, Ricky Andrew starts at full-back, Craig Gilroy, who also represented the Wolfhounds, is selected on the left wing and Michael Allen returns to the province's starting line-up on the right.
With Paddy Jackson on international duty, James McKinney is named at out-half where he will start alongside experienced scrum half Ruan Pienaar.
Tom Court joins recent Wolfhounds debutant Rob Herring and John Afoa in the front row, with captain Johann Muller partnerered by Lewis Stevenson in the second row and Robbie Diack, Sean Doyle and Roger Wilson forming the back row.
Iain Henderson and Luke Marshall have been released by Ireland and are named on the bench. Former Ireland Under-20 full-back Rory Scholes is also named as a replacement and is in line to make his league debut.
Friday's match is a sell-out, the ninth game that has been sold out at Ravenhill this season.
There are fewer than 500 tickets remaining for next week's RaboDirect PRO12 game against the Scarlets. Tickets can be purchased via Ticketmaster or at ulsterrugby.com.
ULSTER (v Ospreys): Ricky Andrew; Craig Gilroy, Jared Payne, Darren Cave, Michael Allen; James McKinney, Ruan Pienaar; Tom Court, Rob Herring, John Afoa, Johann Muller (capt), Lewis Stevenson, Robbie Diack, Sean Doyle, Roger Wilson.
Replacements: Niall Annett, Callum Black, Ricky Lutton, Iain Henderson, Nick Williams, Paul Marshall, Luke Marshall, Rory Scholes.