The green and whites will be looking for a return to winning ways after suffering a first defeat in four on the road at Crawley Town on Saturday.
Carl Dickinson’s goal proved to be the only consolation in the 3-1 defeat, with Darren Way’s side now facing a second successive trip away from Somerset.
The green and whites will do so with a fairly depleted squad, unable to call on up to nine players in Essex.
Stuart Nelson, James Bailey, Francois Zoko, Wes McDonald, Gary Warren, Alefe Santos, Diallang Jaiyesimi and Omar Sowunmi will all miss the midweek encounter, with Alex Pattison needing assessment after withdrawing in the first half at the Checkatrade.com Stadium.
The absentees will likely see Academy duo Gabby Rogers and Daniel Ojo claim a spot in the matchday 18 in a week where Town have been revealed to have given more minutes to players aged under 23 than any other club in the top four divisions.
Facing a U’s side who were four unbeaten before Saturday’s narrow defeat at Bury, the Glovers will look to leapfrog their opponents who sit in fifth place and one point ahead.
The obvious threat will be in-form striker Luke Norris who has the best goals per minute ratio in the division with six goals in 460 minutes of action.
Way’s side will be looking for history to repeat itself in Essex after picking up all three points last season.
In snowy conditions, Alex Fisher’s strike was enough to secure the win that took the club’s winning tally to seven.
Colchester still boast the lead with 12 wins to their name along with six draws.
Tuesday’s meeting will be the 26th meeting between the two sides since 1958.
Craig Hicks will take charge of proceedings at the JobServe Community Stadium.
It’ll be his first match involving the Glovers since overseeing the 1-0 FA Cup win over Southend United at Huish Park in November 2017.
Mr Hicks will be assisted by Carl Fitch-Jackson and Callum Walchester with Graham Kane acting as fourth official.
On matchday, minute-by-minute updates will be provided on YTFC’s official Twitter account and live matchday centre.
If you’re unable to attend the game, domestic and overseas supporters can watch to the game live via the iFollow Glovers service with match passes available to purchase here for £10.
A full match report will follow on YTFC.net at full time with post-match reaction from the manager and a member of the playing staff following soon after.