Should there be a winner, the side claiming three points would move into the Champions League qualification places overnight.
Match preview
Indeed, despite heading into Friday night's match in 11th place in the table, Mainz could move as high as third in the unlikely event that they beat Koln by three or more goals.
Any win would see them leapfrog their opponents all the way into at least fourth place, though, after their impressive 2-0 win away to Werder Bremen last weekend kept them within touching distance of the top half of the table.
Only reigning champions Bayern Munich had scored more goals than Bremen prior to the clash, yet Bo Svensson's side ended a winless run of four games and became only the second team to shut their opponents out this season in the process.
Strikes from Marcus Ingvartsen and Lee Jae-sung either side of half-time proved to be the difference between the sides on the day, with Mainz happy to soak up plenty of possession and hit their opponents on the break.
They may have to be more proactive on home soil at the MEWA Arena on Friday, but they should be boosted by their victory last weekend - as well as their 3-0 win away to VfB Lubeck in the DFB-Pokal in midweek - with the prospect of climbing at least seven places in the table to further incentivise them.
Likewise, Koln can move from seventh to third in the table by beating Mainz on Friday, having returned to winning ways with a 3-2 victory against Augsburg last weekend.
Steffen Baumgart's side fell behind after only 14 minutes to Florian Niederlechner's strike, but Steffen Tigges and Denis Huseinbasic turned the match on its head after half-time before Daniel Caligiuri levelled the proceedings once more.
Tigges, who had only bagged one goal in six appearances prior to the victory, made himself a hero with an 81st-minute winner. It was richly deserved for the hosts having dominated with 65% possession and 15 shots across the course of the match.
Having finished seventh in a hugely successful first season with Koln, Baumgart is still learning how to juggle domestic and continental action with this team, with Koln facing a hugely important Europa Conference League fixture against FC Slovacko on Thursday as they look to chase down the top two teams in Group D.
In the meantime, though, The Billy Goats can dream of qualifying for the Champions League for the first time in their history in what looks set to be an incredibly open Bundesliga season, but only a win against Mainz would see them move into the top four prior to Saturday's action.
Mainz 05 Bundesliga form:
W
L
D
L
D
W
Mainz 05 form (all competitions):
L
D
L
D
W
W
FC Koln Bundesliga form:
W
L
D
W
L
W
FC Koln form (all competitions):
D
W
L
L
L
W
Team News
Svensson only made three changes for his side's trip to Lubeck in the domestic cup in midweek, with Dominik Kohr, Robin Zentner and Jae-sung likely to return to their side's starting XI against Koln.
Maxim Leitsch and Marlon Mustapha remain sidelined through injury, while Stefan Bell and club captain Silvan Widmer will face late fitness tests having missed the last couple of matches through muscle strains.
Koln, meanwhile, should head into the match fresher having been knocked out by Jahn Regensburg on penalties in the first round of the DFB-Pokal.
Baumgart could name the same starting XI which defeated Augsburg last weekend with one notable exception given that Florian Kainz will return from suspension after his red card in the defeat to rivals Borussia Monchengladbach. Eric Martel may make way for the winger.
Mainz 05 possible starting lineup:
Zentner; Fernandes, Hack, Caci; Da Costa, Kohr, Stach, Caricol; Jae-sung, Burkardt; Onisiwo
FC Koln possible starting lineup:
Schwabe; Schmitz, Kilian, Hubers, Hector; Skhiri; Huseinbasic, Duda, Kainz; Tigges, Maina
We say: Mainz 05 1-1 FC Koln
There is very little to split these two sides - who have both hugely improved in the last 18 months or so - and as such we can envisage a share of the spoils on Friday.
Although the incentive of moving up to a top four position may spur both teams on to go for the win, neither are likely to be too disappointed with avoiding defeat in the end.