Merrett (ankle) and Patfull (broken jaw) have missed four matches each since hurting themselves in the team's Round 8 clash against Adelaide at the Gabba.
The pair will be welcome additions to an in-form Lions backline which held reigning premiers Hawthorn to only seven goals in their last outing.
The team will still be without creative half-back flanker Josh Drummond who has failed to overcome a calf strain suffered three weeks ago.
Troy Selwood comes out of the side after dislocating his shoulder in the Lions’ last match against the Hawks in Tasmania while veteran utility Tim Notting has been omitted.
The Lions’ full team to face Melbourne is listed below:
B: Jason Roe (29), Daniel Merrett (21), Jed Adcock (7)
HB: Joel Patfull (24), Lachlan Henderson (14), Joel Macdonald (26)
C: Albert Proud (2), Simon Black (20), Daniel Rich (10)
HF: Michael Rischitelli (35), Jonathan Brown (16), James Polkingorne (31)
F: Rhan Hooper (33), Daniel Bradshaw (36), Luke Power (6)
Foll: Mitch Clark (1), Cheynee Stiller (32), Justin Sherman (11)
Int: Ashley McGrath (9), Scott Harding (5), Jared Brennan (17), Sam Sheldon (3)
Emerg: Jack Redden (30), Matt Austin (37), Tim Notting (8)
IN: Daniel Merrett, Joel Patfull
OUT: Troy Selwood (shoulder), Tim Notting (omit)