The pair have been heading in opposite directions recently, with the hosts winless in five games and the visitors aiming to prolong an unbeaten streak.
Frankfurt are playing their first match of the European season, having qualified directly for the group stages with a fifth-placed finish in last season's Bundesliga.
They were unfortunate to miss out on the Champions League - finishing just one point behind Wolfsburg in fourth - but will now be focusing on their first appearance in European competition since losing in the 2019-20 Europa League round of 16 against Basel.
This year's Bundesliga campaign has not begun well, though, with new boss Oliver Glasner not enjoying the best of starts in Frankfurt since joining from Wolfsburg in the summer.
His new side are winless in their opening five competitive matches, with two defeats followed by three draws.
The most recent came on Sunday at home to Stuttgart, where it looked as though Filip Kostic had grabbed a 79th-minute winner, only for the visitors to equalise in the 88th minute and ensure that Die Adler remain down in 15th, just outside the relegation zone.
They will be looking to bounce back with a strong showing on Thursday, in front of what will likely be a partisan crowd.
Frankfurt have some of the most passionate supporters in Germany, but the atmosphere may be even more fervent than usual for this game on account of their visitors.
Not only does the city have a significant Turkish community, Fenerbahce may also be fielding a famous German international with Turkish roots - their new captain Mesut Ozil.
The former Arsenal creator and his team have enjoyed a far better start to this season's league campaign than their hosts, winning three and drawing one of their first four games to sit third in the Super Lig table.
Unlike their upcoming opponents, the Yellow Canaries did have to progress through a qualifying tie to reach the group stages, but made light work of it as they dispatched Finnish side HJK 6-2 on aggregate, and are now unbeaten in 14 games.
New manager Vitor Pereira will be hoping they can carry that good form into this game and snatch an away victory.
A rare positive note for the hosts, though, was Serbia international Kostic's return to the starting XI against Stuttgart.
They can also take solace in knowing that Fenerbahce too have a significant list of issues - all of which are injuries.
Defender Marcel Tisserand limped off at the weekend and joins an already bloated recovery room, with Jose Sosa, Nazim Sangare, Ferdi Kadioglu and Irfan Can Kahveci all out with muscle problems, and Serdar Dursun absent for another couple of months with a broken collarbone.
Eintracht Frankfurt possible starting lineup:
Trapp; Durm, N'Dicka, Hinteregger, Lenz; Sow, Hrustic; Hauge, Kamada, Kostic; Borre
Fenerbahce possible starting lineup:
Bayindir; Tisserand, Kim, Szalai; Sangare, Sosa, Gustavo, Kadioglu; Osayi-Samuel, Samatta, Ozil
We say: Eintracht Frankfurt 2-1 Fenerbahce
Despite their current poor form, Frankfurt will likely control the game for long periods and should be able to convert a couple of the chances that they create.
Fenerbahce are not known to be good travellers, and could well see their long unbeaten streak come to an end here.
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