Wales lock Jake Ball and flanker Justin Tipuric will miss the Test against South Africa in Cardiff due to injury.
Ball suffered a dislocated shoulder in the 33-18 defeat to world champions New Zealand at the Principality Stadium last weekend and faces a prolonged spell on the sidelines, the Welsh Rugby Union said on Tuesday.
Tipuric, who had only returned from injury against the All Blacks, is out again, this time with a quad injury.
Halfback Rhys Webb is undergoing concussion protocols after a knock in last Saturday's Test and has not been ruled out yet but is doubtful.
Wales have released prop Tomas Francis, five-eighth Rhys Priestland and centre Owen Williams back to their English clubs as Saturday's Test falls outside of the end-of-year window for internationals.
But forwards Taulupe Faletau and Scott Andrews, who also play their club rugby in England, have been allowed to remain with the squad.
"We're a little bit down but it's a chance for other guys," assistant coach Neil Jenkins told a news conference.
"We've got plenty of players, not as many as we had at the start, but we've had a few injuries and hopefully other players can show what they're all about. We've been together for four weeks, most of the stuff we want is in place."
Wales have struggled in their three November Tests, starting with a 29-21 loss to Australia and playing a second-string team that beat Georgia 13-6 before losing to the All Blacks.
