The hosts come into this one following a defeat to Accrington Stanley, while the visitors enter the fray off the back of a stalemate at home to Stevenage.
Match preview
Cambridge have endured a poor 2022-23 campaign so far and sit just one place above the League One relegation slots on 20 points from 19 matches played.
Manager Mark Bonner has a challenge on his hands to secure their league status, with his side winning just one match in their last five attempts in all competitions.
Their last victory came in the FA Cup first round against Curzon Ashton, where the Yellows needed penalties to book their place in round two, following two dismal 0-0 draws against National League North opposition in the first match and subsequent first-round replay.
Last season, Cambridge managed to carry themselves to the fourth round of the competition with some impressive results, notably a 1-0 triumph over Newcastle United, before crashing out in the next stage to Luton Town.
Bonner will hope his side can muster some inspiration from their 2021-22 cup exploits as they look to turn their shaky season around starting on Saturday.
Grimsby travel to the Abbey Stadium in an inconsistent run of form, finding themselves 16th in the League Two standings with Paul Hurst at the helm.
Nevertheless, a thumping 5-1 victory over Plymouth Argyle meant the Mariners secured progress to the second round of the cup, which they will look to build on away to Cambridge this weekend.
They have only won one match in their last six encounters, but managed to gain a 1-1 draw against Stevenage last weekend thanks to a 91st-minute Niall Maher equalising effort.
Positively, Grimsby have already surpassed their efforts in the 2021-22 FA Cup, when they were defeated 1-0 by Kidderminster Harriers in the first round proper.
Hurst will be eyeing a shock result to take them into the third round of the competition, where a potential glamour tie could await should they get the better of Cambridge.
Cambridge United FA Cup form:
D
W
Cambridge United form (all competitions):
W
L
D
D
W
L
Grimsby Town FA Cup form:
W
Grimsby Town form (all competitions):
L
W
W
L
D
L
Team News
Hosts Cambridge will be without midfielder Adam May, who is ruled out for the tie with a long-term cruciate ligament injury.
Paul Digby is at risk of suspension should he pick up a yellow card during the match, while striker Joe Ironside is expected to lead the attack for Cambridge.
Saikou Janneh may be preferred to James Brophy on the left flank, while Shilow Tracey could be given an opportunity in attacking midfield against Grimsby.
For the visitors, they may look to field a relatively strong side as they target a cup upset at the Abbey Stadium this weekend.
Max Crocombe is likely to continue in goal, while Niall Maher will continue following his heroics against Stevenage. Keyendrah Simmonds could be promoted to a starting position up front at the expense of Otis Khan.
Brendan Kiernan could pick up a suspension if he is booked during proceedings.
Cambridge United possible starting lineup:
Mannion; Williams, Okedina, Jones, Dunk; Simper, Digby; Janneh, Tracey, Knibbs; Ironside
Grimsby Town possible starting lineup:
Crocombe; Waterfall, Maher, Smith; Efete, Clifton, Morris, Green, Amos; McAtee, Simmonds
We say: Cambridge United 1-0 Grimsby Town
In a match that could help to turn round the fortunes of both Cambridge and Grimsby, we expect a cagey affair as both sides are low on confidence due to recent results.