The hosts will be looking to exact revenge on their visitors following a narrow 2-1 defeat in the reverse fixture back in early October.
Match preview
Colchester United had to settle for a share of the spoils from their encounter against Mansfield which ended in a 1-1 stalemate at the One Call Stadium on Saturday.
Danny Cowley's men took the lead in the 12th minute through Harry Anderson before relinquishing their advantage to Lewis Brunt 20 minutes into the second period.
As a result, The U's remain bottom but two in the League Two table, just one point clear of the drop zone, albeit with three matches in hand.
Coming up next is the challenge of an opposing outfit who have been beaten in just one of the last eight editions of this fixture since 2020.
Winless in five straight home matches since the turn of the year, Tuesday's hosts will be keen to get back to winning ways in front of their fans.
Newport County saw their two-game winning streak come to an end against Barrow following a 1-0 defeat at Holker Street on Saturday afternoon.
Graham Coughlan's men trailed to Cole Stockton's opener just shy of the midway point of the first half and that proved to be the all-important moment.
With 55 points picked up from 39 matches so far, The Ironsides sit 11 in the standings, four points behind Crawley Town in the race for the final playoff spot.
Having split their last six away outings into three wins and three losses apiece, Tuesday's visitors will be looking to string together a decent run of form on enemy territory.
Colchester United League Two form:
D
D
D
L
D
D
Newport County League Two form:
W
L
L
W
W
L
Team News
Newport County's Omar Bogle remains unavailable for selection due to a long-term knee injury which has seen him fail to feature since Boxing Day.
Defender Declan Drysdale also misses out for the away side as he prepares to sit out a third consecutive game due to a muscle problem.
Twenty-year-old Samson Tovide will be pushing for a place in the starting XI after making his return to action for Colchester last time out.
Alistair Smith has played every game for the hosts since joining from Lincoln City on loan and the Englishman is expected to get the nod once again.
Colchester United possible starting lineup:
Goodman; Hall, Dallison, Mingi; Fevrier, Read, McGeehan, Smith, Anderson; Hooper, Ihionvein
Newport County possible starting lineup:
Townsend; Jameson, Bennett, Bright; Lewis, Morris, Wildig, Charsley, Payne; Evans, Palmer-Houlden