Jordan Henderson and Raheem Sterling have withdrawn from the England squad to return to their respective clubs for assessments on potential injuries.
Henderson, 30, came off at half-time in the defeat to Belgium complaining of tightness in his leg, according to Three Lions boss Gareth Southgate.
And Sterling, 25, missed the Nations League clash altogether with what was described as a “small” injury.
The Reds have seen first-choice centre-backs Virgil van Dijk and Joe Gomez ruled out with long-term knee injuries within the last month.
Elsewhere, right-back Trent Alexander-Arnold suffered a calf injury during the 1-1 draw with Manchester City and is facing another fortnight on the sidelines.
And left-back Andy Robertson is a doubt for the Premier League tie with Leicester on Sunday after sustaining a tight hamstring while away with Scotland.
Their issues stretch beyond the defence too, with Mohamed Salah currently in self-isolation after testing positive for coronavirus while on international duty with Egypt.
How will England fare against Iceland on Wednesday in the absence of Jordan Henderson and Raheem Sterling? Have your say here.
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Meanwhile, City boss Pep Guardiola will hope to have Sterling available for the trip to second-place Tottenham.
Southgate insisted the winger had been left out as a precaution and hoped he would return to full fitness “by the end of the week”.
The England boss said: “Raheem felt something a couple of days ago and didn’t train on Friday as a precaution.
“He started training yesterday and wasn’t really happy with it. We have discussed it and it isn’t one to take a chance on.
“I think he will be fine by the end of the week, but the games for us just came too quickly.
“It was a slightly heavy pitch when we trained on Friday and it is a small niggle really. He had a good rest at the beginning of the week – a bit of an unfortunate incident but not one that is going to keep him out for long.”
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