London - Wales lock Luke Charteris has been ruled out of the Six Nations international against France in Cardiff on Friday with a knee injury, the Welsh Rugby Union said Tuesday.
His place in coach Warren Gatland's starting XV has been taken by Bradley Davies.
Gatland has made two other changes to the side that beat Scotland 27-23 at the Millennium Stadium 10 days ago, with wing Alex Cuthbert and flanker Dan Lydiate drafted into the New Zealander's run-on team.
Meanwhile, in a positional switch, Wales captain Sam Warburton moves to openside flanker from blindside, with Justin Tipuric dropped to the bench.
Behind the scrum, centre Jonathan Davies has been given the all-clear after missing French club side Clermont's Top 14 match against Castres last weekend because of a groin problem.
But Charteris, who also plays his club rugby in France, has not recovered in time after being sidelined from duty with Paris-based Racing 92 last Saturday.
Cuthbert has been given his first start of this Six Nations in place of Cardiff team-mate Tom James, who is now no longer even in the matchday 23.
"We have made a couple of changes, one injury enforced with Luke missing out with a knee injury, but Bradley deserves a starting spot as well, so it's a good opportunity for him," said Gatland in a WRU statement.
"We have made two other personnel changes, with Alex and Dan coming into the starting team. They have trained well and will suit the game France will potentially bring as well."
Wales were not due to reveal their team until Wednesday but Gatland, explaining the change, said: "We initially thought we would have to wait until later in the week to have a final update on injuries, but we know where we are earlier than expected and have told the squad, hence announcing (the team) today (Tuesday) as well."
Wales, who drew against defending champions Ireland in their opening fixture of this season's Six Nations, face a France side bidding to make it three wins out of three under new coach Guy Noves after victories over Italy and Ireland.
However, Wales have not lost to France since an agonising 2011 World Cup semi-final defeat in Auckland - a match where Warburton was sent off - and have won their last four Six Nations clashes against 'Les Bleus'.
"France come to Cardiff unbeaten in the campaign so far, and impressing under Guy (Noves)," said Gatland.
"We are looking to continue our unbeaten run and will be looking for another step up after the victory over Scotland," he added.
Wales: 15 Liam Williams, 14 Alex Cuthbert, 13 Jonathan Davies, 12 Jamie Roberts, 11 George North, 10 Dan Biggar, 9 Gareth Davies, 8 Taulupe Faletau, 7 Sam Warburton, 6 Dan Lydiate, 5 Alun Wyn Jones, 4 Bradley Davies, 3 Samson Lee, 2 Scott Baldwin, 1 Rob Evans
Substitutes: 16 Ken Owens, 17 Gethin Jenkins, 18 Tomas Francis, 19 Jake Ball, 20 Justin Tipuric, 21 Lloyd Williams, 22 Rhys Priestland, 23 Gareth Anscombe