The 39-year-old former Manchester United striker made a goalscoring return for Milan as a substitute against Lazio on Sunday, coming on to tap in the second goal in a 2-0 Serie A victory.
That followed a four-month knee injury lay-off, and the Swedish frontman has now reportedly suffered discomfort in an Achilles, forcing him out of plans for Wednesday's Anfield tussle.
That means coach Stefano Pioli will name Ante Rebic or former Arsenal and Chelsea striker Olivier Giroud as his attacking spearhead when he selects his side to face Jurgen Klopp's Reds.
Pioli stated Giroud would not be able to play a full 90 minutes, having returned from a spell on the sidelines after testing positive for COVID-19.
Speaking in a news conference on Tuesday, Pioli said: "Zlatan has had an inflammation; he gave it a go this morning but it's useless to take risks at this point of the season.
"I see AC Milan with Zlatan and I absolutely think we'll have him back soon. Absences are a part of football; I'll need to choose between Ante and Olivier but we have the cover."
Ibrahimovic has abundant Champions League experience, scoring 48 goals in the competition from 120 games, with nine of those coming for Milan between 2010 and 2012 in a previous spell with the Rossoneri.
Milan are in the Champions League for the first time in eight years with last term's second-placed finish in Serie A.
They last featured in the competition in the 2013-14 campaign, a worrying drought for the club that have won the event on seven occasions.
"Our growth over the past year is clear for all to see," Pioli said. "Our experiences have helped us to grow and improve, and the beginning of this season has shown that this team knows how to play and how to approach games.
"The level is higher now; it's what we wanted and it's a chance for us to show that we can mix it with the best."
