Max Evans moves to the wing to replace Danielli, with De Luca forming a centre partnership with Graeme Morrison.
Fly-half Dan Parks will win his 50th cap as the Scots aim for their first win of this year's tournament.
Scrum-half Chris Cusiter has shaken off a virus to continue in his role as captain of Andy Robinson's side.
John Barclay has also recovered from a knee knock to continue in an impressive back row with Glasgow team-mates Kelly Brown and Johnnie Beattie as the Calcutta Cup goes up for grabs for the 127th time.
A return for experienced lock Nathan Hines had been widely anticipated but Jim Hamilton, all 19st, 12lb of him, retains his starting place after playing in the defeats to Wales and Italy.
Hines, who lost his place to injury after the opening loss to France but returned to the bench in Rome, is again among the replacements, with Danielli swapping places with De Luca.
Rory Lawson, Geoff Cross and Alan MacDonald are drafted in as substitutes, replacing injured trio Mike Blair, Alasdair Dickinson and Alasdair Strokosch.
Scrum-half Blair and prop Alasdair Dickinson both suffered concussion in their weekend club matches, while Dickinson's Gloucester team-mate Strokosch is struggling with the recurrence of an ankle injury.
Thom Evans and Rory Lamont were also unavailable to Robinson through injury.
"The team has played some good rugby and we have been creating chances," said Robinson. "We just need to take that next step and finish off a game.
"Max has been our most potent attacker and we also want to see Nick and the qualities that he can bring to this game."
15 Hugo Southwell (Stade Français)
14 Sean Lamont (Scarlets)
13 Nick De Luca (Edinburgh)
12 Graeme Morrison (Glasgow Warriors)
11 Max Evans (Glasgow Warriors)
10 Dan Parks (Glasgow Warriors)
9 Chris Cusiter (Glasgow Warriors)
1 Allan Jacobsen (Edinburgh)
2 Ross Ford (Edinburgh)
3 Euan Murray (Northampton Saints)
4 Jim Hamilton (Edinburgh)
5 Alastair Kellock (Glasgow Warriors)
6 Kelly Brown (Glasgow Warriors)
8 Johnnie Beattie (Glasgow Warriors)
7 John Barclay (Glasgow Warriors)
Substitutes
16 Scott Lawson (Gloucester)
17 Geoff Cross (Edinburgh)
18 Nathan Hines (Leinster)
19 Alan MacDonald (Edinburgh)
20 Rory Lawson (Gloucester)
21 Phil Godman (Edinburgh)
22 Simon Danielli (Ulster)