London - Australia flank David Pocock will miss Saturday's match against England at Twickenham, team management said on Tuesday.
The world-class back-row forward had been due to return to action this weekend following knee ligament damage, but a scan on Monday confirmed Pocock had suffered a calf strain which ruled him out of the Cook Cup clash.
Australia will also be without lock Kane Douglas, who suffered a knee injury in last Saturday's 33-6 defeat by France in Paris.
The tourists could lose another second row if Rob Simmons is banned by a disciplinary hearing on Wednesday after being cited for a dangerous tip tackle during the France match.
Douglas has had a highly eventful tour. He played against France despite the news his mother, Trish, had been taken ill on the flight over from Australia on Friday.
While still in a London hospital, Mrs Douglas is listed as being in a comfortable condition.
Both Pocock and Douglas will have their injuries re-assessed next week when the squad has arrived in Italy ahead of the third match of the Wallabies' tour, against the Azzurri in Florence.