David Amoo and Kyle Howkins are doubtful when Cambridge host Colchester in League Two on Saturday.
Midfielder Amoo and defender Howkins, who is on loan from West Brom, are struggling with hamstring injuries.
Striker Jabo Ibehre shrugged off a rib issue to start and play 60 minutes of the midweek Checkatrade Trophy match at Northampton, which Cambridge lost on penalties. And defender Brad Halliday returned following appendicitis last week against Morecambe and is set to continue.
But defender George Taft could make his debut after signing on loan from fellow League Two side Mansfield until January.
Colchester could have five new faces on show after signing ex-Wigan winger Sanmi Odelusi on a free transfer and adding four players on loan, including midfielder Brandon Comley from QPR.
Odelusi, 24, has agreed a deal until the end of the season while Comley, 21, will stay with the U's until January.
Crystal Palace defender Ryan Inniss, 22, has signed on a season-long loan, with striker Brandon Hanlan, 20, joining from Charlton until January. Forward Nicke Kabamba, 24, has signed on loan until January from Portsmouth.
Colchester could restore several players after dispatching Reading Under-21s in their Checkatrade match. Sam Walker could return in goal with Frankie Kent, Tom Lapslie and Kyel Reid in contention.