The reigning champions lost Nathan Ake to an unspecified issue in the first half of Sunday's 0-0 draw with Arsenal, where Kyle Walker (thigh) and Ederson (thigh) were already absent.
Guardiola was none the wiser about the nature or severity of Ake's concern after the game, but with just two full recovery days to play with, it would be a surprise to see the Dutchman passed fit for the midweek battle.
The Citizens did unexpectedly have John Stones at their disposal on Sunday, as the England international took his seat on the bench for the Arsenal stalemate, despite Guardiola professing that he would definitely miss the match on Friday.
However, Stones was only an unused substitute and is not quite back to full fitness yet, so Rico Lewis should be given the nod to replace Ake, as was the case in the first half of the Easter Sunday showdown.
With Lewis operating at right-back, Ruben Dias and Manuel Akanji ought to form Stefan Ortega's central barrier, as Josko Gvardiol continues on the left after keeping a fatigued Bukayo Saka quiet.
Mateo Kovacic also performed relatively well during his 61-minute cameo against the Gunners, and another start for the Croatian alongside Rodri and Kevin De Bruyne is not beyond the realm of possibility.
Guardiola may be tempted to freshen up the wide areas with the reinstatements of Jeremy Doku and former Villa hero Jack Grealish, though, thereby demoting Phil Foden and Bernardo Silva down to the bench.
Erling Haaland got no change out of William Saliba or Gabriel Magalhaes at the weekend, but despite the threat of Julian Alvarez, the Golden Boot winner ought to hold his position at the tip of the 4-2-3-1.
Manchester City possible starting lineup:
Ortega; Lewis, Dias, Akanji, Gvardiol; Rodri, Kovacic; Doku, De Bruyne, Grealish; Haaland