McDonald has been named in the starting 18, while Fitzpatrick is on the extended bench.
And rookie Tom McNamara, who has made three appearances for the Demons, is also a chance to play his first match since round 21, 2009.
But Melbourne has lost forward Ricky Petterd with a quadriceps injury.
As expected, the Demons have lost Aaron Davey and Colin Sylvia through suspension.
Davey is out for one week, while Sylvia will miss the rest of the season, having been rubbed out for two matches.
Defender Luke Tapscott, who missed last round with a hip injury, has been rushed back into the 18.
Midfielder/forward Neville Jetta has also been named in the starting line-up.
He will play his first match since round 12, after being sidelined with hand and shoulder injuries. Jetta has since worked his way back via the VFL.
Dasher Daniel Nicholson has also been included in the initial squad.
On the extended bench is Cale Morton, Jordie McKenzie, Joel Macdonald, McNamara, Jeremy Howe, Nicholson and Fitzpatrick.
Utility Jamie Bennell will play his 50th AFL match against the Suns.
Melbourne
B: Colin Garland, James Frawley, Clint Bartram
HB: Luke Tapscott, Jared Rivers, Tom McDonald
C: Sam Blease, Brent Moloney, Jack Trengove
HF: Tom Scully, Stef Martin, Brad Green
F: Liam Jurrah, Jack Watts, Jamie Bennell
FOLL: Mark Jamar, Neville Jetta, Nathan Jones
I/C (from): Cale Morton, Jordie McKenzie, Joel Macdonald, Tom McNamara, Jeremy Howe, Daniel Nicholson, Jack Fitzpatrick
IN: Tom McNamara, Luke Tapscott, Jack Fitzpatrick, Neville Jetta, Tom McDonald, Daniel Nicholson
OUT: Aaron Davey (suspension), Colin Sylvia (suspension), Ricky Petterd (quadriceps)
NEW: Tom McDonald, Jack Fitzpatrick