McGregor, who has been a nearly constant presence on the pitch, was missing from the lineup as Celtic played in the Scottish Cup Glasgow derby.
The club’s fans were quick to notice his absence in the crucial match.
O’Neill revealed that McGregor’s previous game against Aberdeen had taken its toll on the skipper, leaving him too sore to take to the pitch today.
O’Neill told BBC Scotland: “Yes it is (an injury).
“He was feeling pretty sore by the end of the Aberdeen game and he’s just not recovered in time.
“It’s a big blow.
“It’s a blow to us.
“He’s the captain in every aspect of it, both a leader in the dressing room and on the field. He’ll be a big miss for us.
“You have to accept it. Things like this happen in football and you’ve got to get on with it.”
Kasper Schmeichel, too, is off the roster today, with the manager reporting he remains in recovery following a recent injection.
Regarding Schmeichel, O’Neill stated: “Recovery yes, from the injection as well too, so I just thought we’d give it a little bit more time.”
Liam Scales, playing at left-back in the absence of Kieran Tierney, takes the armband.
Scales has been allocated the left-back position, replacing Kieran Tierney who remains sidelined due to a foot injury he sustained against Aberdeen.
The midfield also saw changes, comprised as it was today of Luke McCowan, Reo Hatate, and Benjamin Nygren.