The U's will be without Jabo Ibehre after the striker saw red just before half-time in Tuesday's goalless draw at Hartlepool following a challenge on defender Neil Austin.
Manager Joe Dunne stressed post-match that he would be launching an immediate appeal against the harsh decision but, on further inspection of the rulebook this week, he has decided not to do so and Ibehre will now start a three-match suspension.
His unavailability comes as a blow at a time when Freddie Sears is again ruled out with the knee injury that forced him to miss the game at Victoria Park altogether, with Colchester now without their two leading goalscorers against the Alex.
But Dunne has moved to bolster his attacking options with the loan capture of Troy Hewitt from QPR until the end of the season and the striker is set to make his debut.
Captain Kem Izzet got another 90 minutes under his belt for the club's Under-21 side in midweek following his ankle injury and will hope to make the matchday 18.
Crewe boss Steve Davis retains major doubts over the fitness of on-loan Newcastle midfielder Brad Inman.
The Railwaymen are looking to bounce back from consecutive defeats to the U's fellow strugglers Hartlepool and Portsmouth, and Inman sustained ankle damage against the former.
"Brad is still out but he is making good progress and it is nothing too serious," Davis told his club's official website.
"He should be out for a week or so, so we'll have to see with him."
With the exception of rookie defender Jon Guthrie, who will miss the rest of the campaign after undergoing hernia surgery, Davis has no other injury worries as he looks to secure the victory that will take his side to the much-desired 50-point mark.
"I've pushed them hard this season, more than I did last season and they have done superbly well so far," he added.
"But we want to push on and finish as we possibility can. The first priority is still 50 points and safety."