Seamus Coleman picked up a hamstring injury against Liverpool and his return date is unknown.
Replacing the skipper’s leadership won’t be easy, but given the team is playing with confidence, there should be no shortage of team-mates ready to step up and set the standards.
Meanwhile, there appear to be two main candidates to replace the Irishman at right back.
As per TeamTalk, Carlo Ancelotti said he expects to have academy graduate Jonjoe Kenny back for the trip to Southampton on Sunday, while Ben Godfrey came on to replace Coleman on Saturday.
How do the two promising English defenders compare?
Kenny is probably the natural replacement and went into the season at Coleman’s deputy, as underlined by his selection at right back in the EFL Cup.
That was before he suffered an injury against West Ham and the question for Ancelotti is whether to throw him straight back into the fray after that setback.
If Kenny is fully fit and ready, his attacking intent would ably replace Coleman’s on the right of defence.
He has had to wait patiently for his Premier League opportunity but impressed out on loan at Schalke last season.
22-year-old Godfrey is not a right back by trade and has only played there three times in his career; with one of those coming on Saturday.
He has the advantage of being fully fit, and to a certain extent, also being the man in possession of the shirt after impressing against Liverpool.
With James Rodriguez free to roam inside, perhaps a steady, unambitious right back option behind him isn’t the end of the world.
But he remains an awkward fit, a central defender out of position in a wide area and Southampton’s flying wingers Nathan Redmond and Theo Walcott may identify that as an area which can be exploited on Sunday.