The hosts are looking to bounce back from consecutive defeats in League One, while their fourth-tier opponents have the chance to claim a third successive victory.
Match preview
Shrewsbury may be pleased to turn their attention to FA Cup action after experiencing a couple of poor results in the league.
Matt Taylor's side saw a three-game unbeaten league run ended by a 3-0 away defeat against Barnsley, before they lost 2-0 to Wigan in a game where they were forced to play with 10 men following Chey Dunkley's fourth-minute red card.
Those two away defeats saw Shrewsbury slip down to 18th position in the League One table with 17 points to their name from 18 games.
They will be glad to return home to New Meadow, where they currently enjoy a four-game unbeaten run in all competitions.
Having progressed from the first round in the last nine seasons, Saturday's hosts will be quietly confident about their chances of making it through to the second-round draw.
Colchester, meanwhile, have experienced a tumultuous few weeks, which began with the sacking of Ben Garner last month.
After overseeing just three wins in the opening 13 league games of the season, Garner was dismissed and replaced by interim boss Matthew Etherington.
The 42-year-old manager guided the team to a 3-2 victory over Grimsby Town in his first game in-game, but he was forced to step aside from his role ahead of Saturday's meeting with Accrington Stanley due to a contract dispute with his former club Crawley Town.
In Etherington's absence, the U's went on to claim a narrow 1-0 victory over Accrington thanks to a second-half effort from Joe Taylor.
While Crawley maintains that Etherington is still under contract with them, Colchester chairman Robbie Cowling has reinstated the interim boss following legal advice, ensuring the former Stoke City player will be in the dugout for Saturday's first-round clash.
Shrewsbury Town form (all competitions):
L
W
D
W
L
L
Colchester United form (all competitions):
L
L
W
L
W
W
Advert - content below:
Team News
Taylor has confirmed that Shrewsbury midfielder Kieran Phillips is set to be out for around three months with a knee injury.
The Shrewsbury boss is also unable to call upon the injured trio of George Nurse, Ryan Finnigan and Morgan Feeney.
Brandon Fleming, who has missed the last two matches, remains a doubt for Saturday's encounter, while Dunkley is suspended after being sent off last weekend.
As for the visitors, they are expected to be without Nico Lawrence, Fiacre Kelleher, John Akinde and Ellis Iandolo due to injury issues.
Owura Edwards is also in the treatment room after recently suffering a knee injury, which will keep him out of action for two months.
While Etherington was not in the dugout at the weekend, he could opt to select an unchanged lineup following Saturday's narrow win over Accrington.
Shrewsbury Town possible starting lineup:
Marosi; Anderson, Flanagan, Sraha; Winchester, Kenneh, Perry, Benning; Bayliss; Bowman, Udoh
Colchester United possible starting lineup:
Goodman; Greenidge, Mitchell, Hall, Egbo; Tovide, Read, McGeehan, Fevrier; Chilvers; Taylor