Cardiff - England lock Courtney Lawes will miss the rest of the Six Nations after straining his calf during Saturday's 21-13 defeat to Wales, the Rugby Football Union announced on Sunday.
The 30-year-old Northampton second row was replaced by Brad Shields with just a few minutes left to play at the Principality Stadium in Cardiff, shortly before Wales' Josh Adams scored the try that put the result beyond doubt and extinguished England's hopes of a Grand Slam with two rounds left to play.
"Courtney Lawes (Northampton Saints) will miss the rest of the Guinness Six Nations due to a calf strain sustained yesterday in Cardiff," said the RFU statement.
"Following the results of his scan this (Sunday) afternoon, Lawes is expected to be out for a minimum of four weeks. He will return to his club for rehabilitation."
Lawes will now miss out the Twickenham clashes with Italy and Scotland on March 9 and 16 respectively.
Saturday's match also saw England wing Jonny May leave the field with suspected concussion.
It leaves England, who could yet win the Six Nations title, with a growing injury list after prop Mako Vunipola, who didn't play against Wales, had already been ruled out of the remainder of the tournament with an ankle problem.
Meanwhile former captain Dylan Hartley has not featured at all this Six Nations after the hooker was sidelined with a knee injury.
Lawes' absence may at least be offset by the return of fellow lock Maro Itoje, who suffered knee ligament damage during England's tournament-opening win over champions Ireland.
"We've lost three of our best forwards and we've got to be able to cope with that," said England coach Eddie Jones.
"Maro's coming along well. He might have a chance against Italy."