The hosts haven't played for over two weeks, since they beat Chelsea U21's 4-0 in the Football League trophy, while the visitors squeezed past AFC Wimbledon in the same competition, in a rescheduled fixture on Wednesday.
Match preview
Following promotion to League One last season, Cheltenham Town will be looking to improve on a 15th-placed finish, the highest in the third tier of English football in club history.
Since then, talented manager Michael Duff has left the club, after he helped the club to win the League Two title and secure that record finish, allowing former Burnley midfielder Wade Elliott his first senior coaching role.
The Robins find themselves in 17th, five points above the drop zone, despite having scored the fewest goals in the division this campaign.
Striker Alfie May has not quite been able to replicate his 23-goal season this time around, unable to shake off reoccurring injuries, but with three in his last four League One outings, there are signs that Cheltenham's talisman is creeping back into form.
Plymouth, on the other hand, have been rampant this season in League One, sitting pretty at the top of the table, locked in a tussle for the title with Ipswich Town.
Following a run of seven victories in eight games, Steven Schumacher's men have hit a slightly trickier patch of form in November and December, winning just one of their last five league encounters, before falling to their first home defeat of the season to Port Vale.
The Pilgrims also made hard work of League Two side AFC Wimbledon on Wednesday, as a second-half Sam Cosgrove hat-trick saw The Argyle come from three goals down to force extra time and penalties, against a side 35 places below them in the English football pyramid.
A trip to shot-shy Cheltenham perhaps represents a good chance to get back into more convincing winning ways.
Cheltenham Town League One form:
W
D
D
W
W
L
Cheltenham Town form (all competitions):
D
W
W
W
L
W
Plymouth Argyle League One form:
W
D
D
L
D
W
Plymouth Argyle form (all competitions):
D
W
L
D
W
D
Team News
Cheltenham will continue to be without both Will Ferry and Taylor Perry, as they near a return to fitness from back and hamstring injuries respectively.
Following a brace in the EFL trophy last time out, Charlie Brown could well be given a chance to impress here, alongside Dan N'lundulu and May.
For the visitors, important defender James Bolton has resumed full-contact training after breaking his foot bone back in March, although this trip could come too soon.
Fellow centre-back Brendan Galloway will be out until at least February with a hamstring tear, while important midfielder Finn Azaz targets a late January return.
Cheltenham Town possible starting lineup:
Southwood; Williams, Freestone, Taylor, Long, Broom; Bonds, Sercombe; Brown, N'Lundulu, May
Plymouth Argyle possible starting lineup:
Cooper; Mumba, Gillesphey, Scarr, Lonwijk, Edwards; Houghton, Randell; Whittaker, Ennis, Cosgrove
We say: Cheltenham Town 1-2 Plymouth Argyle
With both sides in patchy form, it is difficult to call this encounter with much conviction, but ultimately, the quality of the league leaders should tell.
Plymouth have suffered with defensive injuries of late, so we can see the home side getting on the scoresheet, but the firepower of the division's top scorers should prove too much.