Wales will take on Scotland at Murrayfield without the services of Gavin Henson after the centre failed to recover from a calf muscle strain.
The Ospreys ace had been selected in the starting XV for what would have been his first appearance since Wales clinched the Grand Slam against France last March.
Since then, he has missed six Tests because of both an ankle injury and an Achilles' problem.
And his injury jinx has struck again with Henson unable to shake off the calf muscle strain he picked up during a training session on Tuesday.
As a result Blues centre Tom Shanklin is called-up off the bench to partner Jamie Roberts in midfield, with Andrew Bishop joining the replacements.
Wales' chances of making a flying start to their Six Nations defence on Sunday have nevertheless received a boost after Scotland lost two key forwards - prop Euan Murray and lock Nathan Hines - because of injuries.
But they have a poor record in Edinburgh since the mid-1980s, winning on just two occasions - in 1997 and 2005.
They lost 21-9 the last time they visited the Scottish capital two years ago.
However, that was before Gatland arrived from New Zealand to help revive Welsh fortunes.
"As players, we don't dwell on what happened two years ago," said Wales prop Gethin Jenkins, who wins his 64th cap this weekend.
"We are a different side playing in a different way to two years ago.
"We did not go up there with a lot of confidence after losing to Ireland at home. We did not perform."
Such has been the intensity with which Gatland has prepared his players for this weekend's match that Wales actually had to step back in training this week, for fear of peaking too soon.
Jenkins added: "The non-playing weeks where there is no Test match at the end of it are always mentally and physically tiring.
"We were really beasted in training sessions on Wednesday and Saturday last week, and it was good to get back to those levels of intensity.
"This game against Scotland is massive for us. We rate them highly and they have really improved since last season's Six Nations, which they showed during the autumn.
"They competed well as a pack against South Africa and New Zealand, and you measure yourself against the Tri-Nations sides.
"We have to make sure the Welsh set-piece performs."