Hartlepool were without Cooke for their 2-0 home defeat to Woking – their first defeat at the Suit Direct Stadium this season.
Cooke has been a regular for Hartlepool under John Askey this season, scoring two goals in his first eight appearances of the campaign.
But the midfielder is now set to join the likes of Dan Dodds and Anthony Mancini in missing a prolonged period through injury after picking up an ankle problem in training.
Both Dodds and Mancini are to miss the rest of the season after suffering ACL and hamstring injuries respectively and Cooke is now also set to miss a number of months after rolling his ankle.
"Callum looks like he’s going to be out for a while,” Askey confirmed.
"It was a nothing incident. There was nobody anywhere near him. It was at the end of training and he’s gone over on his ankle and heard a crack so it looks quite serious."
And when pressed for a timeframe on the 26-year-old’s return Askey said: “It will probably be months.”
It represents another major blow for Hartlepool’s chances this season, with Askey already seeing his squad stretched to its limit just two months into the campaign.
But Askey has insisted the injuries to key players cannot be used as an excuse for any loss of form moving forward.
"It’s happening every week. We’re having no luck at the moment with regards to injuries, but we can’t use those things as an excuse,” he said.
"We all know they’re not just three players, they’re three very good players. At the start of the season it looked completely different but we should still have enough out there to compete.
"The players who go out there have got to do better. We’ve got to fight and battle. We know we’ve got goals in us. The hardest thing to do is score goals, the easiest thing is to keep them out I always thought, until this year.”