Wales scrumhalf Rhys Webb was ruled out of the Rugby World Cup on Tuesday with a "significant midfoot injury."
The Welsh Rugby Union announcement came a day after saying fullback Leigh Halfpenny will miss the tournament starting next week with a right leg injury.
Both were injured and carried off on a cart on Saturday in the 23-19 warm-up win over Italy at Cardiff.
Webb's left leg was trapped in a ruck in the first half. He needed more examination on his foot and knee before more details could be revealed.
"It is extremely disappointing for both Leigh and Rhys," coach Warren Gatland said in a statement. "They have worked exceptionally hard to establish themselves on the world stage and to prepare for the tournament, and we wish them all the best with their recovery."
Scrumhalf Mike Phillips and winger Eli Walker were summoned as their replacements.
Phillips has played 99 tests, five for the British Lions, and will appear at his third World Cup. He was the backup in 2007 and starter in 2011, and first choice from 2008 until last year, when his skills faded.
In contrast to Phillips' experience, Walker has played only once for Wales, last month against Ireland at home in a warm-up, a 35-21 loss.
"After announcing the squad, we spoke about the need for players to remain ready for action and this is a great opportunity for Mike and Eli," Gatland said. "It's great that we can call on players of this calibre. To bring Mike's experience into the squad is a bonus, along with Eli's exciting talent."
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