Key players James Frawley (pectoral), Michael Newton (broken wrist) and Ricky Petterd (hamstring) are all injured, while Nathan Jones (soreness) and Mathew Warnock will also miss the round-robin clash against Adelaide and Port Adelaide.
The key omissions have paved the way for Melbourne to unveil their first round selection from the 2010 NAB AFL Draft, Lucas Cook.
The tall forward will be joined by another young forward prospect, Jeremy Howe, who will also play his first game in senior AFL company.
Talented young midfielder Sam Blease will finally get his chance at senior level after spending the past two years battling injury.
The Demons face Adelaide first up on Friday night, with the Crows welcoming back a host of players who were struck down with injury last year.
Defender Andy Otten returns from a yearlong stint on the sideline with a knee injury, while Chris Knights, Daniel Talia and Brad Moran have all been named in the NAB Cup squad.
Midfielders David Mackay (groin) and Bernie Vince (knee) won't take part as they recover from their respective injuries.
Port Adelaide will be the second side to take on Melbourne and coach Matthew Primus will be keen to get his squad through unscathed.
The Power have the longest injury list out of all the clubs with key players Travis Boak, David Rodan and Jacob Surjan set to miss the opening round of the NAB Cup.
In good news for Port Adelaide, the club will unveil its 2009 top-10 draftee, John Butcher, whose first AFL season was cruelled by a back injury.
The key forward will make his long awaited first senior outing on Friday night along with talented young ruckman Jarrad Redden, Aaron Young and rookies Mitch Curnow, Daniel Webb and Jarrad Irons.
