The Iron will be seeking to double their points tally in Group H of their Checkatrade Trophy campaign on Tuesday night when Grimsby Town visit Glanford Park (7.45pm kick-off).
A further derby encounter against Doncaster Rovers (away) follows at the end of the month, but victory would confirm United's progression to the next round of the competition.
Should Rovers also triumph against Sunderland U21s, the Black Cats and the Mariners will both be eliminated from the trophy with one group match still to play.
United manager Graham Alexander indicated in his pre-match press conference that he will once again make changes, as he did for the Sunderland U21s encounter in August.
Andrew Crofts is cup tied after playing for Charlton Athletic in their first group stage game, while Charlie Goode, Luke Williams and Jonathon Margetts will continue to sit out with their respective injuries.
The two sides last met in the FA Cup in 2013 when Grimsby Town went through to round two following a replay at Glanford Park.
The initial fixture at Blundell Park was goalless before the Mariners won 2-1 ten days later.
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Grimsby manager Russell Slade stated in his pre-match press conference that he will make wholesale changes for the game, but will start Harry Clifton and Karleigh Osborne.
Osborne, 29, played for Brentford between 2005 and 2012 making 161 appearances. He also played for Millwall and Bristol City, amongst others, before arriving at Blundell Park in July. The central defender is in line to make his fifth appearance for the club.
ELSEWHERE IN THE CHECKATRADE TROPHY...
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