The club's only win over Welsh opposition this season was the 21-19 reverse over Cardiff Blues in September, and they will face a much sterner assessment from an Ospreys side enjoying a five match winning streak in the tournament.
The Welshmen are fifth on points' difference alone, with a win capable of lifting them into a top four play-off place for the first time this season.
Edinburgh Rugby head coach, Michael Bradley, said: "We return for the first match in the 'second phase' of the season and look to get moving against a formidable opponent in the shape of the PRO12 champions.
"They come here full of confidence having won five on the bounce in the league and will be keen to maintain their run and underline their championship credentials.
"Both matches last season were close affairs; at Liberty Stadium they cleared their lines and ran the full length to score in the last minute and here, at Murrayfield, they edged us by a single point, thanks to the converted try-of-the-season from [Hanno] Dirksen.
"What is frustrating is that in the league this season we have been a score a-drift on four occasions, a narrow gap which we must crack tomorrow night.
"This match is hugely important to our season. It's up to us to put a marker down and start this phase of the season on the front foot."
The home side's changes are evenly split between the forwards and backs.
Hooker Ross Ford returns from Scotland duty to start in place of the injured Andy Titterrell (hamstring) and packs down between props John Yapp and Willem Nel.
Izak van der Westhuizen and Perry Parker form a new look second-row, while the back-row of Sean Cox, Roddy Grant and Stuart McInally remains unchanged.
Sep Visser (wing) and Dougie Fife (outside-centre) replace the injured Lee Jones and John Houston, who moves to the bench, with James King (inside-centre) earning reselection after an impressive return against Ulster.
Scrum-half Richie Rees trades places with Chris Leck to line-up next to stand-off Gregor Hunter, while Greig Tonks and Tom Brown keep their places in the back three.
Edinburgh Rugby team to play Ospreys at Murrayfield (kick-off 7.05pm) in RaboDirect PRO12 round nine.
15 Greig Tonks
14 Sep Visser
13 Dougie Fife
12 James King
11 Tom Brown
10 Gregor Hunter
9 Richie Rees
1 John Yapp
2 Ross Ford
3 Willem Nel
4 Perry Parker
5 Izak van der Westhuizen
6 Sean Cox CAPTAIN
7 Roddy Grant
8 Stuart McInally
Substitutes
16 Alun Walker
17 Allan Jacobsen
18 Lewis Niven
19 Robert McAlpine
20 Hamish Watson
21 Chris Leck
22 John Houston
23 Mike Penn
Absent through injury: Ben Atiga (knee), Ben Cairns (knee), Dimitri Basilaia (knee), Jamie Farndale (leg), Lee Jones (groin), Steven Lawrie (knee), Ross Rennie (shoulder), Netani Talei (knee), Andy Titterrell (hamstring), Steven Turnbull (knee)
Absent on international duty: Geoff Cross, Nick De Luca, David Denton, Grant Gilchrist, Greig Laidlaw, Matt Scott, Tim Visser
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