Wales are going for a third outright title in a row following their triumphs in 2012 and 2013, something never previously achieved in the tournament's history.
But head coach Gatland's selection is likely to include players who are not certain to be fully fit for their opening game against Italy on February 1.
It also comes at a time when the Welsh game is riven by a civil war between the Welsh Rugby Union and the four professional regions, which may ultimately end in a courtroom battle.
Chief among Gatland's injury concerns is captain Sam Warburton.
The Lions skipper has not played since suffering a shoulder problem in the autumn defeat to Australia, and Cardiff Blues boss Phil Davies has stated he is a couple of weeks away from fitness, giving him little time to find form before facing the Azzurri.
Prop Gethin Jenkins is also doubtful after he picked up a leg injury in the Blues' Heineken Cup defeat to Toulon at the weekend, with a scan set to reveal the severity of the problem.
Centre Jonathan Davies remains sidelined with the pectoral injury suffered against South Africa in November and is set to miss at least the first three games of the Six Nations.
Blues fly-half Rhys Patchell is another long-term absentee thanks to knee and shoulder issues, with his regional colleague Cory Allen another to be sidelined.
Jamie Roberts missed the entire autumn campaign but is set to return from an ankle injury for Racing Metro this weekend, while Newport Gwent Dragons forward Andrew Coombs should also be in contention despite suffering a broken nose at the weekend.
Back-rower Ryan Jones, meanwhile, has not played since Boxing Day due to a hamstring injury.
On the plus side for Gatland, wing George North has excelled for Northampton over the last few weeks, with the Lions star running in a stunning solo try against the Ospreys on Sunday.
Scott Williams' form suggests he will be a capable stand-in for Davies in midfield, while Mike Phillips has settled quickly at Racing Metro after being sacked by Bayonne towards the end of last year.
Behind Phillips the scrum-half pecking order is tough to decide, with Lloyd Williams, Rhys Webb, Gareth Davies and Rhodri Williams all pushing for inclusion.
Fly-half is similarly competitive, with Dan Biggar, Rhys Priestland and James Hook all vying for the starting role, while Leicester's Owen Williams and Ospreys Sam Davies may also come under consideration.
Scarlets prop Samson Lee looks set to earn a call-up after an impressive run of recent performances anchoring the west Wales' region's scrum, with Ospreys lock James King, Dragons wing Hallam Amos and Blues centre Owen Williams all in contention for squad berths.