De Zeeuw has been troubled by the same knee for a large chunk of the season, his training carefully managed to make sure he is ready for Premiership action.
But he aggravated the injury after landing awkwardly following a header in the Liverpool penalty area.
Manager Paul Jewell said: "It must be quite a serious problem because Arry had to come off which is not like him.
"We're getting the knee scanned today and we'll know more once that is done."
If de Zeeuw is facing a spell on the treatment table, it will leave Latics short of cover at the back.
Jackson and Stephane Henchoz are the only two senior centre-halves available in the squad, as Emerson Thome fractured his cheekbone in last week's Carling Cup win over Newcastle.
Right-back David Wright could provide cover but he's currently out on a month's loan at Norwich City having not played a league game for Latics this season.
Jewell will be hoping de Zeeuw can shake the injury off with away games at Chelsea and Manchester United coming up. And in the longer term, there's the busy Christmas programme to get through before the squad can be bolstered in the January transfer window.
Latics' 3-0 defeat at Liverpool on Saturday saw them drop to seventh place in the table, and Jewell admitted his side had been very much second best to the European champions.
But he remains content with their points tally after 14 games and has again asked for the club to be judged on a full season rather than at this stage of the campaign.
Jewell said: "It was really hard work watching that, especially the first half.
"It was so unlike us. One thing you can normally guarantee with us is that we give everything.
"But for some reason in the first half we looked frightened and sat off Liverpool which wasn't the thing to do.
"Liverpool went on to win the game easily and that was very disappointing as far as I'm concerned.
"We were better in the second half, but there's nothing we can take from the first.
"At the moment we're in a tough run of matches and we knew that was always going to be the case.
"Maybe some people were getting ideas above their station after we got 25 points from 11 games.
"I kept talking about survival, which might have sounded negative, but I knew what we were coming up against.
"We're new to the Premiership and up against world class players every week, so it was always going to be tough.
"It will get even tougher for us if we play like we did in the first week, but thankfully that seems the exception to the rule.
"This is a long old season and we have to be pleased with 25 points so far."
Away from the Premiership, Latics have landed themselves two home matches in the Carling Cup and FA Cup.
Local rivals Bolton Wanderers will visit later this month in the quarter-finals of the Carling Cup, with the clash on either December 20 or 21.
And yesterday's FA Cup draw produced a tasty third-round pairing with Leeds United who are currently pushing for promotion from the Championship.
That game is due to be played on Saturday, January 7.