It was a minor miracle Ajax qualified for the competition given the season they had last year, but they look set to be competitive this time around.
Match preview
The Dutch giants spent a substantial chunk of last season in the bottom half of the Eredivisie, but eventually recovered to finish fifth, ensuring European football again at the Johan Cruyff Arena.
On matchday one, they looked imperious, thrashing Besiktas 4-0 in a game where they could have racked up plenty more goals, keeping Mert Gunok busy in the visiting goal.
Their strong rearguard also impressed, as that game was the first time in three years that they have stopped their opponents having a shot on target - which peculiarly also came against Besiktas.
It was also Ajax's seventh European game of the season already, as they had to come through qualifiers against Vojvodina, Panathinaikos and Jagiellonia Bialystok to get this far.
Playing all of those qualifiers mean Ajax are lagging behind in the Eredivisie, having only played five league games instead of seven, but they have already dropped five points - losing to NAC Breda and drawing with Go Ahead Eagles.
However, Francesco Farioli made a name for himself by building a superb defence at Nice last season, and it looks like he is doing the same here, as Ajax have conceded just once in five games.
Therefore, this game could see them end a run of 14 away European games without a clean sheet, a run which has seen them concede 29 goals, and not keep a team at bay on their travels in three-and-a-half years.
The visitors will also be hoping that can lead them to a first win on Czech soil in their history, because despite their illustrious history, Ajax have not tasted victory on six previous away matches against clubs from the country.
Even if that run does continue though, on paper Ajax will surely have enough to progress given the sides they have been drawn against, as they should be able to reach a double-figure points tally after facing Qarabag, RFS and Maccabi Tel-Aviv.
Slavia will be keen to build momentum in what is a huge week for the Czech club, facing European royalty before the Prague derby at the weekend.
The hosts have won 12 of their 14 games this season in all competitions, and are three points clear of rivals Sparta Prague at the top of their domestic league.
However, the one defeat on their record so far came against Lille in the Champions League playoffs, and even though they won the second leg, Jindrich Trpisovsky was astounded looking on from the touchline at how his side did not progress.
Slavia had to settle for the Europa League, but they made a strong start, winning 2-0 away to Ludogorets Razgrad on matchday one thanks to goals from Matej Jurasek and Mojmir Chytil.
That saw them keep yet another clean sheet, as almost eight hours of action have passed since Slavia conceded a goal, coming back in August on that fateful night against Lille.
The Cervenobili have faced Dutch sides on seven occasions in Europe, but Ajax are the only one they have managed to beat, doing so in both legs of their 2007 Champions League qualifier, while the two met once more in the UEFA Cup group stage a year later, and shared the spoils in a 2-2 draw in Amsterdam.
Slavia Prague Europa League form:
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Slavia Prague form (all competitions):
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Ajax Europa League form:
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Ajax form (all competitions):
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Team News
Slavia have a long list of players absent heading into this fixture, with Czech trio Lukas Masopust, Tomas Vlcek and Lukas Vorlicky all currently sidelined.
A fractured cheekbone will keep Nigerian Igoh Ogbu out for a few weeks, while Slovakia's Euro 2024 star Ivan Schranz has also spent an extended time out injured.
Goalkeeper Jindrich Stanek is also unavailable at present, while Petr Sevcik is not registered in Slavia's European squad.
On the field, only three players have scored more Europa League goals than Chytil since he made his competition debut last season (five), and the Slavia forward is averaging a goal every 86 minutes, after notching on matchday one.
Ajax's long run through qualification means they already have a player suspended due to yellow card accumulation, as Jorrel Hato collected his third of the season against Besiktas.
At 19, Mika Godts became the second-youngest Ajax player to score a European double last midweek, after Ton Blanker did the same all the way back in 1979 just 100 days younger, and the impressive young Belgian should feature again after getting a slight rest at the weekend.
On the injury front, Steven Berghuis is the big miss at present, joining Anton Gaaei and Sivert Mannsverk on the treatment table, but Gaston Avila is closing in on a return after a lengthy absence with a knee injury.
Slavia Prague possible starting lineup:
Kinsky; Holes, Zima, Boril; Doudera, Zafeiris, Dorley, Diouf; Chytil, Chory, Provod
Ajax possible starting lineup:
Pasveer; Rensch, Sutalo, Baas, Wijndal; Fitz-Jim, Henderson, Taylor; Traore, Brobbey, Godts
We say: Slavia Prague 2-2 Ajax
Slavia have won 11 of their last 14 home games in Europe, and Ajax have never won away in the Czech Republic, but that does not mean this will be a foregone conclusion.