Jan-Moritz Lichte's side suffered a 2-1 defeat to Arminia Bielefeld in their most recent outing, whereas Koln played out a 2-2 draw with high-flying Wolfsburg.
Mainz finally appeared to have turned the corner after claiming their first point of the 2020-21 Bundesliga campaign at the seventh attempt last month, with a draw with Schalke preceding a win over Freiburg and another stalemate with Hoffenheim.
Jan-Moritz Lichte's men had a prime opportunity to go a fourth game unbeaten when they faced off against newly-promoted Arminia - who have also struggled for goals and results this season - but Mainz fell to a 2-1 defeat to the 2019-20 2.Bundesliga champions last Saturday.
Kevin Stoger came off the bench to net his first goal of the season in that game, but the damage had been done early on after Ritsu Doan and Manuel Prietl both bagged for Arminia to bring Mainz crashing back down to earth after a respectable run of results.
Things were starting to look up for Die Nullfunfer after the win at Freiburg, but Mainz were given a harsh dose of reality against Arminia and still sit in the relegation zone, with the woeful and winless Schalke the only side to have accumulated fewer points than Lichte's men after 10 games.
This weekend's hosts have a chance to climb out of the bottom three with a win if Arminia also lose to Freiburg, but should Mainz suffer defeat and Schalke somehow prevail at Augsburg, Lichte's men will finish the weekend at the bottom of the pile.
Koln's overall results makes for bleak reading for the Billy Goats, but Markus Gisdol will no doubt be feeling pleased after two impressive results against sides in the top five.
Gisdol's men won their first game of the season at the ninth attempt, but it was one worth waiting for as Koln triumphed 2-1 on Borussia Dortmund's turf, and the Billy Goats also managed to take a point from their clash with an unbeaten Wolfsburg side last Saturday.
Ondrej Duda and Jan Thielmann both struck for Gisdol's men in that four-goal thriller, but while Koln have now only tasted defeat twice in their last seven outings, a superior goal difference is the only thing keeping them out of the bottom three at present.
The other bottom-of-the-table clash between Freiburg and Arminia will have a huge impact on the standings by the close of play this weekend, and Koln could finish this weekend as high as 14th or as low as 17th depending on results.
Mainz marched to a 3-1 victory in this fixture last season before playing out a 2-2 draw on Koln's turf, and the Billy Goats have not triumphed over Die Nullfunfer since the 2016-17 campaign.
Mainz 05 Bundesliga form: LLDWDL
FC Koln Bundesliga form: DLDLWD
Mainz right-back Daniel Brosinski did not take part in the loss to Arminia owing to gastrointestinal problems, but the 32-year-old is now fit again and ready to be called upon.
However, the same cannot be said for Levin Oztunali, who is expected to remain sidelined with a thigh injury until the new year.
Koln midfielder Salih Ozcan had to come off just before the 40-minute mark in the draw with Wolfsburg, but the 22-year-old has been training since and should be fine for this six-pointer.
A further boost for the visitors is captain Jonas Hector making his return to team training, and the midfielder is in contention to feature against Mainz.
Mainz 05 possible starting lineup:
Zentner; St-Juste, Niakhate, Hack; Brosinski, Fernandes, Barreiro, Martin; Boetius, Quaison; Mateta
FC Koln possible starting lineup:
T. Horn; J. Horn, Bornauw, Cestic; Skhiri; Wolf, Ozcan, Rexhbecaj, Jakobs; Thielmann, Duda
We say: Mainz 05 1-2 FC Koln
Both of these strugglers have been showing the early signs of a welcome revival in recent weeks, and the two managers should set their sides up to attack in what is certainly a winnable game for both Mainz and Koln. However, the confidence will be much higher in the visitors' camp in comparison to a Mainz side who just lost to one of the newly-promoted teams, so we are tipping the Billy Goats to come up trumps on Saturday.