WillGriff John and Will Rowlands have been ruled out of Wales' match against Australia at the Principality Stadium on Saturday with concussion.
Both players have been released from the squad after sustaining head injuries in last weekend's win against Fiji.
Prop John and lock Rowlands were forced off as Wales secured a 38-23 victory.
The news will come as a blow to Jonathan Humphreys and his injury-ravaged squad following a punishing Autumn Nations Series campaign.
John's fellow tighthead Tomas Francis is following return-to-play protocols after being concussed in training last week.
Wing Josh Adams, who was withdrawn from the starting line-up just before kick-off against Fiji due to a calf muscle issue, is also being monitored ahead of the Wallabies clash, along with No.8 Aaron Wainwright (shoulder).