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The defender was carried off off during Saints' 2-1 defeat to Hibernian in the Clydesdale Bank Premier League.
McGregor was out for seven months with cruciate ligament damage sustained in his other knee a year ago.
Lennon told the club's website: "Darren had a scan on his knee today and we are now waiting on the full report.
"That being said we are 95% - although we await confirmation - that he has damaged his cruciate in the other knee from the one that was injured last season.
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"It's a big blow for all concerned - for Darren, the club and the fans."
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