The England international hurt his hamstring in the 2-0 win over Aston Villa before the two-week hiatus, and Slot has confirmed that he is yet to resume team training and therefore should be spared for the clash with Real Madrid next week.
Alexander-Arnold joins Alisson Becker (thigh), Diogo Jota (abdominal) and Federico Chiesa (fitness) as the Reds' definite absentees, but Harvey Elliott (foot) is training again, and Virgil van Dijk has been given the all-clear after returning early from Netherlands duty.
The Dutchman should therefore be fine to join fellow regulars Ibrahima Konate and Andrew Robertson at the back, while Conor Bradley and Caoimhin Kelleher will deputise for Alexander-Arnold and Alisson respectively.
There should be no respite for Alexis Mac Allister and Ryan Gravenberch in the engine room either, unless Slot opts to start Curtis Jones in a deeper role following the former's return from South America.
However, the Englishman is flourishing further forward and could keep Dominik Szoboszlai at bay once more, joining Mohamed Salah and Darwin Nunez in the Liverpool forward line.
As ever, Slot's biggest quandary comes on the left-hand side of the attack, where Cody Gakpo may just edge out Luis Diaz if the Colombian is kept in bubble wrap for the visit of Madrid.
Liverpool possible starting lineup:
Kelleher; Bradley, Konate, Van Dijk, Robertson; Mac Allister, Gravenberch; Salah, Jones, Gakpo; Nunez