The England defender suffered a hamstring injury at the Liberty Stadium last week and has not recovered in time to be in contention for the Reds' visit to Stamford Bridge
The full-back has been in impressive form this season but injured his hamstring at Swansea last Saturday and did not feature in Wednesday's Champions League win over Shakhtar.
The Blues are second in the Premier League and just a point behind leaders Manchester United, but Cole's absence is an untimely blow as they seek to regain top spot with a victory over Brendan Rodgers' men.
Ryan Bertrand, viewed by many at Stamford Bridge as Cole's long-term successor, deputised during the Shakhtar clash and will likely fill in on the left again against Liverpool.
But Di Matteo has stated his hope that the 31-year-old will be available for selection for next weekend’s game against West Brom, who are now managed by former Chelsea assistant Steve Clarke.
Cole has made 10 appearances for the Blues this season, scoring once and getting two assists – although he faced a fine from the FA after a controversial Twitter outburst in October.
The defender's contract expires in the summer and, with no new deal seemingly forthcoming after a breakdown in talks, could be set to move on at the end of the current campaign.