Saturday's lacklustre 1-0 loss to Norwich dropped Arsenal to ninth in the English standings, with even manager Arsene Wenger acknowledging the performance was a "shock to the system."
However, the team remains in a strong position after winning its first two group matches in the Champions League and a victory at the Emirates Stadium would put the Gunners on the brink of qualification.
"It is a good lesson, but I would have preferred not to get it," Wenger said of the Norwich match. "Because if you need lessons like that you will stand there at the end of the season and be full of regrets. I hope it will have a positive impact."
Montpellier hosts Olympiakos in the other Group B game, with both teams looking for their first wins to jump into contention for a top-two finish.
Schalke, which reached the Champions League semifinals in 2011, is second in the group with four points and comes into the match buoyed by a 2-1 win over rival Borussia Dortmund in the Bundesliga on Saturday.
"I think it was the first big game we played in which we showed what we can do," Schalke striker Klaas-Jan Huntelaar said.
The win ensured Schalke moved five points clear of the defending champions.
"We played a fantastic game and were able to put the opponent under pressure," Schalke defender Benedikt Hoewedes said. "We also tried to play football."
Schalke is the only Bundesliga team that has yet to lose a competitive game away from home this season, but the club has not won in England in five attempts.
"We shouldn't get carried away," Hoewedes said with an eye on Wednesday's game. "It won't be easy for us. In London we'll have to throw everything into the pot (but) with our fans behind us, I'm sure we can get a good result."
Highly rated 19-year-old attacking midfielder Julian Draxler is doubtful after breaking his left wrist in the 2-2 draw against Montpellier.
Greece defender Kyriakos Papadopoulos returned to training Sunday after 2 1/2 weeks out with chicken pox, but there are still questions over the 20-year-old player's fitness for the match against Arsenal.
Both sides will have the same coaches in charge from their previous meetings in 2001-02 — when Arsenal secured a 3-2 win at Highbury before losing 3-1 in Germany — with Huub Stevens now in his second stint at Schalke and Arsene Wenger a fixture in north London.
"Our young team is still developing," Stevens said after Saturday's win in Dortmund. "But (the players) have shown what they are capable of."