Liverpool have drifted to as big as 2/1 with some bookmakers to retain the Premier League title as Jordan Henderson and Andy Robertson became the latest players to be struck down by injury.
Scotland captain Robertson missed Sunday's game in Slovakia because of a hamstring injury before Henderson was substituted midway through England's 2-0 defeat in Belgium.
Jurgen Klopp could hardly have envisaged a worse international break, with Joe Gomez having already undergone knee surgery that will rule him out for the majority of the season and Mo Salah testing positive for Covid-19.
Klopp will be hoping the rest of his players can emerge from the final set of midweek international fixtures unscathed, with the small matter of Premier League leaders Leicester visiting Anfield on Sunday.
Prior to the international break, the Liverpool boss had claimed he had no plans to sign a new defender in January despite the loss of Virgil van Dijk for what is expected to be most of the season.
Napoli's Kalidou Koulibaly and RB Leipzig centre-back Dayot Upamecano are two of the names being linked with a move to Merseyside, and Klopp could be forced to change his mind.
On top of the injuries already mentioned, midfielder-turned-defender Fabinho - Van Dijk's most likely replacement - has not played since limping off against Midtjylland in October.
Joel Matip only recently returned from his own injury problems to make just his third appearance of the season away at Manchester City - his two previous run-outs were followed by month-long lay-offs.
That draw at the Etihad saw Trent Alexander-Arnold suffer a calf problem in the closing stages to add to the champions' woes.
Premier League winner odds
- Man City - 11/8
- Liverpool - 13/8
- Chelsea - 8/1
- Tottenham - 10/1
- Leicester, Man Utd - 28/1
- Arsenal - 66/1
Odds correct at 09:50 16/11/20
Click here for the full current Sky Bet market
While the focus of Liverpool's issues is rightly on their defence, Henderson's potential absence adds to a growing absentee list in midfield too.
Thiago hasn't played since being hurt by a terrible last-minute Richarlison challenge in the Merseyside Derby on October 17, his first start for the club having been unable to build on an impressive debut as a substitute against Chelsea because of a positive Covid-19 result.
England midfielder Alex Oxlade-Chamberlain has not played a single minute this term after sustaining a knee injury during pre-season.
The one area of the pitch where Liverpool have depth currently is in attack, largely thanks to the form of summer signing Diogo Jota but also the impressive cameo displays of Xherdan Shaqiri.
That being said, any team would miss Salah, especially when the Egyptian has scored eight goals in eight Premier League starts this season.
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