The Colts head coach has been undergoing treatment for leukaemia since the fourth week of the current season, leaving offensive coordinator Bruce Arians in charge.
Arians told the Indianapolis Star: "[It's] still up in the air, later this week, hopefully, we'll be able to know something for sure.
"[Pagano] feels great. Looks good. [Blood] counts were good. We've got our fingers crossed.
"The perfect timing would be [for Pagano to] come in Christmas Eve. It would be a great Christmas present for all of us. That's what our goal is. Hopefully he can start Monday."
The Colts face the Houston Texans in their final regular season game, and can seal a place in the playoffs with a win this weekend.