Chelsea captain John Terry has been ruled out of action for up to three weeks after the club confirmed he underwent surgery on his injured knee.
Terry (left) and Cole missed England's Euro 2008 clash with Russia
Chelsea have also confirmed full-back Ashley Cole will be out for around four weeks after injuring his ankle while on England duty last weekend.
Both players missed Wednesday's 2-1 Euro 2008 qualifying defeat to Russia.
Boss Avram Grant said: "John's had an operation and Ashley is also injured and likely to be out for four weeks."
Terry missed last week's 3-0 win over Estonia with the injury and then aggravated the problem in training, forcing him to sit out the defeat to Russia which hit England's hopes of qualifying for next year's European Championships.
He had only just returned from a broken cheekbone, but will now miss the Premier League games against Middlesbrough, Manchester City and Wigan, as well as the Champions League
showdown with Schalke.
Grant added: "John had a problem and tried his best to be available for the national team but in the last moment of the training, he got injured again.
"He has had an operation and will be out for two or three weeks."
It is the worst possible preparation ahead of Saturday's visit to Boro, but the Israeli is confident he has a big enough squad to cope.
Either Tal Ben Haim or Alex will deputise for England skipper Terry and Grant said: "We have a big squad and we need to handle this situation."