The 22-year-old Jason Harris-Wright will make his first competitive start for Leinster at hooker in a front row which includes props Heinke van der Merwe and Clint Newland.
Former Ireland Under-20 hooker Harris-Wright had a 40-minute runout against the Newport Gwent Dragons last Saturday and now has five Leinster caps to his name.
Isa Nacewa, who lies in second place in the Magners League top points scorers list this season (80 points), continues at full-back in a back-three completed by Andrew Conway and Shane Horgan, who scored a brace of tries in Leinster's bonus point victory over the Dragons.
In all, Leinster coach Joe Schmidt has made five changes to the team that secured that 27-6 win. Conway and Ian Madigan have been added to the back-line, taking over from David Kearney and Shaun Berne on the left wing and at out-half respectively.
Richardt Strauss, Trevor Hogan and Rhys Ruddock make way in the forwards, with Harris-Wright, O'Donoghue and Dominic Ryan getting starting berths.
Speaking ahead of Sunday's clash, recent debutant Newland said that he was pleased to make a winning start to his Leinster career against the Dragons.
"I thought last week's game went okay. The play around the park was quite quick and the only thing I found to be a bit strange was the scrums. All of the techniques and that are a bit different over here compared to back home," explained the New Zealander.
"I'm enjoying the Leinster set-up and all the boys have been really good to get on with. The two games in five days will be a test of our resources, but from what I've seen I reckon the boys will handle that okay. All of our training has been quite sharp lately."
Newland added: "I had been playing over in New Zealand for 12 years and I thought that now was a good time for a change. So far I'm glad that I made the change. I've enjoyed my time at Leinster so far and I just hope that it carries on.
"No, I haven't been rubbing it in (about New Zealand's win over Ireland)! I actually thought that Ireland played quite well and if a few things had gone their way then the scoreline could have been a lot closer. So, yeah, I've been keeping rather quiet!"
LEINSTER (v Ospreys): Isa Nacewa; Shane Horgan, Eoin O'Malley, Fergus McFadden, Andrew Conway; Ian Madigan, Isaac Boss; Heinke van der Merwe, Jason Harris-Wright, Clint Newland, Leo Cullen (capt), Ed O'Donoghue, Dominic Ryan, Shane Jennings, Stephen Keogh.
Replacements: Tom Sexton, Jack McGrath, Mike Ross, Eoin Sheriff, Rhys Ruddock, Paul O'Donohoe, Ian McKinley, David Kearney.