Adam D'Arcy, Tommy Seymour, David McIlwaine, Johann Muller and Pedrie Wannenburg will all make their league debuts from the start, while replacements Paddy McAllister, Ian Porter and Jonny Shiels are also newcomers to this level.
That makes eight new caps for Ulster, and reflects the injuries, unavailability and squad changes that the management have had to oversee.
Australian triallist D'Arcy retains his place at full-back after an impressive showing in last week's pre-season win over Leeds Carnegie.
Seymour, who starred for the Ulster Ravens last season, switches to the right wing in place of the injured Craig Gilroy (fractured jaw), allowing McIlwaine to come in on the left wing.
The 21-year-old McIlwaine helped Queen's University win the All-Ireland League Division 3 title last May and has been capped by Ireland at underage level.
Paul Marshall returns at scrum half having recovered from a shoulder injury sustained in the opening friendly against Bath last month.
Up front there is no change to the pack that started against Leeds, with Ireland duo Rory Best and Stephen Ferris successfully coming through their first match back - they got 40 minutes each last Thursday - and Springboks Muller and Wannenburg eager for game-time.
"There's expectations on us and that's good - it's something Ulster have never really had over the last number of years.
"It's always been (a case of others thinking), 'there are a lot of young kids up in Ulster - let's see what they can do this year.'
"But with the new signings and that bit of experience, hopefully that will push Ulster forward."
Sizing up the Ospreys, the Lions back rower added: "Apart from last year's defeat we have a pretty good (home) record against the Ospreys. It's always a tight game between us.
"They are littered with international talent. But we are exactly the same this season with our new signings and all the boys in tip-top shape, we're going to give any team a good run."
Meanwhile, Ireland summer tourists Tom Court and Paddy Wallace have been named on the bench, while young prop McAllister, who sustained neck and back injuries against Bath, has been passed fit to play.
ULSTER (v Ospreys): Adam D'Arcy; Tommy Seymour, Darren Cave, Ian Whitten, David McIlwaine; Niall O'Connor, Paul Marshall; Bryan Young, Rory Best (capt), Declan Fitzpatrick, Johann Muller, Tim Barker, Stephen Ferris, Willie Faloon, Pedrie Wannenburg.
Replacements: Nigel Brady, Tom Court, Paddy McAllister, Ryan Caldwell, Robbie Diack, Ian Porter, Paddy Wallace, Jonny Shiels.