Locks Bradley Davies and Luke Charteris have been ruled out for the whole tournament and Alun Wyn Jones will miss at least the opening two matches.
To add to new coach Rob Howley's woes, Ospreys' pair Ian Evans (knee) and Ryan Jones (thumb) are also carrying injuries ahead of the opening match against Ireland at the Millennium Stadium on Febrary 2.
Howley has taken over as head coach while Warren Gatland concentrates on his British and Irish Lions duties. The New Zealander, who will coach the Lions in Australia this year, stepped down during the November internationals.
Evans and Jones were being assessed daily according to Howley.
"We are still very much positive at this moment in time. We will probably be in a better position on Monday," he said.
Howley said Wales had been hit by injuries to key players in the first 20 to 25 minutes during the November tests.
"That is always going to have an influence when your player base isn't large compared to other nations," he said. "We see it as an opportunity for players who are young and talented."
Wales will welcome back Lions tighthead prop Adams Jones, who was unavailable in November through injury.
"When you look at his influence in the world game he's probably one of the best tightheads in world rugby," added Howley.
He said Wales also hoped to have their dynamic flanker Dan Lydiate back into the team towards the end of the tournament. Lydiate, who broke his right ankle in September, was named last year's player of the championship.
"We will take that decision as and when we need," he said. "We feel that in the backrow we have some strength in depth to select from."
In Lydiate's absence, Wales could select Justin Tipuric on the openside, which would mean switching captain Sam Warburton to number six on the other side of the scrum. Warburton said he would be comfortable in either position.
"I would be more than happy to plan anywhere in the back row with Wales," Warburton said on Wednesday. "There's been moments in the game when I've covered six for Wales already."
Warburton said Wales took confidence from last year's performance into the Six Nations despite their poor record since last year's triumph.
The Welsh lost 3-0 in Australia and were then defeated on successive weekends by Argentina, Samoa, New Zealand and Australia, again, in November.
They could, though, have easily won the away series against the Wallabies with better decision making in the final minutes and their loss to Australia in Cardiff came in the last minute.
"That's just the fine line of international rugby. With regards to form going into the Six Nations you have to wait until the first or second game to see who shapes up. It's very hard to predict," said Warburton.
"When you win your first match and your second match it's a great place to come to training in. People are a lot happier and training is a lot more enjoyable.
"I'm sure every nation will be putting a lot of pressure on themselves to make sure they win that first match. We have three games on the road so it will be nice to win at home."
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