Ireland international Conor Murray will make his first start of the season after being a try-scoring replacement against the Dragons.
Murray replaces Peter Stringer at scrum half with the fit-again Denis Hurley and New Zealander Casey Laulala also returning to the starting back-line at full-back and inside centre respectively.
Marcus Horan and BJ Botha make way in the front row for Wian du Preez and Stephen Archer, while Tommy O'Donnell, another of the try scorers against the Dragons, has earned a start at blindside flanker in place of David O'Callaghan.
Donnacha Ryan and Peter O'Mahony are included in a matchday squad for the first time this season, and will hope to have an influence off the bench.
Penney is hoping for another positive result for his side as they build towards the start of the Heineken Cup next month.
"So far I think we're happy where we are. If you take the results and you think about where the team is going, in terms of the rugby stuff that is being delivered, I am over the moon.
"The bonus on the back of that positivity is that we were able to get some results in the early part of the competition, which is all good."
The scrum is an area that the New Zealander would like to see improvements in on Saturday evening, adding: "When we get our scrum right, we're fine, I think there is some technique stuff that teams bring to a game that can be a bit disconcerting.
"We're focusing on us and there are parts of our game we need to get better with. Looking through the whole tournament, there are challenges at scrum time."
Of the players currently ruled out through injury, former captain Paul O'Connell tops that list. Johne Murphy (knee), Felix Jones (shoulder), Luke O'Dea (ankle), Sean Scanlon (back), Ivan Dineen (stomach), Troy Smith (knee), James Coughlan (groin) and Ian Nagle (shoulder) are also currently out of contention.
MUNSTER (v Ospreys): Denis Hurley; Doug Howlett (capt), Keith Earls, Casey Laulala, Simon Zebo; Ronan O'Gara, Conor Murray; Wian du Preez, Mike Sherry, Stephen Archer, Donncha O'Callaghan, Billy Holland, Tommy O'Donnell, Niall Ronan, Paddy Butler.
Replacements: Damien Varley, David Kilcoyne, BJ Botha, Donnacha Ryan, Peter O'Mahony, Peter Stringer, Ian Keatley, James Downey.