Warburton misses Saturday's Millennium Stadium appointment with Italy because of a knee injury, the latest problem following thigh trouble that restricted him to just 40 minutes' action during victories over Ireland and Scotland last month.
Prop Gethin Jenkins will skipper the side in World Cup leader Warburton's absence, with Ospreys flanker Justin Tipuric handed a first Test match start, packing down alongside back-row colleagues Dan Lydiate and Toby Faletau.
Warburton would be a huge loss for the World Cup semi-final re-match, which comes just five months after Wales were knocked out 9-8 by France in Auckland and their captain was sent off.
A Wales victory would then leave them needing to beat France for their third Six Nations title and Grand Slam in eight seasons.
"The medical opinion is that we are very hopeful he (Warburton) will be fit to face France next week," Wales assistant coach Rob Howley said.
Of more immediate concern is the Six Nations favourites putting Italy away to set up next week's full-scale assault on Six Nations silverware.
Howley added: "Patience and composure in the opposition 22 and ball in play time is pretty important, along with accuracy on the ball.
"We have to get the contact area right because international rugby is all about creating quick ball. The quicker the ball, the greater the opportunity we will have to score tries.
"We want to play a tempo, ball-in-hand game, but in order to do that we have to be accurate in our kicking game.
"When you see how Italy have played so far, they have good line speed in defence and we have to be aware of that. It is something we did not deal with well at Twickenham, and we have to put that right tomorrow.
"International rugby is about starting well. We have started all three games well so far, and it was a disappointment that the territory and possession we had in the first 20 minutes at Twickenham did not show on the scoreboard.
"We have to focus on the first 20 minutes, dominating possession and territory. If we are able to do that, the second-half is a little easier. We want to implement our game-plan straight away."
Wales have won five and drawn one of their Six Nations encounters against Italy in Cardiff, averaging almost 40 points a time.
But defence coach Shaun Edwards said: "There will be no complacency tomorrow because the players are all fighting for their places.
"They will want to make sure they hold on to the jersey because we have pressure in virtually every position. No-one wants to lose their spot in the team.
"We are trying to improve with each performance and give of our best.
"We have two home games in front of us, and you have to realise that if you are to win a championship you have to do so in a variety if ways.
"Sometimes you have to grind it out and dig really deep, which we did in Ireland, and throughout a campaign there will be telling moments when you have to adapt to different situations and defences.
"England had incredible line speed in their defence and we had to adapt to that, and Scotland came out fighting in the first-half, but we weathered the storm and dominated the second-half.
"We want to go out there and play attacking, entertaining rugby, and when they (Italy) get the ball we want to attack them with our defence."
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