Jamie Roberts has been ruled out for the next six weeks with an elbow injury.
The Wales and Cardiff Blues centre sustained a hyperextended elbow against Australia last Saturday.
Cardiff's director of rugby Phil Davies said: "Only a fortnight ago things were looking very positive for us, when we were welcoming back some key players.
"However, we have been extremely unfortunate to pick up a raft of injuries in the last few weeks.
"It is frustrating that we cannot select from a full-strength squad for these crucial matches, but on a positive note, it gives a chance for some of our other players to step up and show what they can do."
It is expected that Roberts should be fit again in time for Wales's opening Six Nations match against Ireland on February 2.