Meanwhile, Vitoria sit bottom of Group F having failed to earn a single point from their opening three fixtures.
While an eight-game unbeaten streak gave reason for Unai Emery to be optimistic about the development of his side, the subsequent five-match period has suggested that their earlier spell had simply papered over the cracks.
Courtesy of a dramatic 3-2 triumph over Vitoria at the end of last month, Arsenal are perfectly placed to progress into the last 32 of this competition, but letting slip leads in each of their last three domestic games has put Emery under severe pressure at the Emirates Stadium.
Saturday's 1-1 draw with Wolverhampton Wanderers has left Arsenal six points adrift of the top four, leading to reports that Emery may soon be removed from his position in the dugout.
Another victory over Vitoria on Wednesday afternoon will not do anything to improve Emery's stock at the North London outfit, but defeat would result in more question marks over whether the Spaniard will remain in charge in the long term.
However, while there would have been frustration having only earned a 1-1 draw at Moreirense at the weekend, Vitoria will be in a positive frame of mind heading into the reverse encounter with the English giants.
That will be partly due to twice leading at the Emirates Stadium before falling victim to two free kicks from substitute Nicolas Pepe in the closing stages.
A win would have arguably represented the most famous result in their history, although there will be no-one associated with Os Conquistadores who will not feel that they can cause a big upset in front of their own supporters this week.
Vitoria de Guimaraes form: LDLLWD
Arsenal form: WLWDDD
Having missed the last two matches due to the fallout from his angry outburst towards supporters against Crystal Palace, Granit Xhaka could be handed a recall for this contest.
Marcus Edwards will hope to be given another start for Vitoria, with the former Tottenham Hotspur youngster having scored at the Emirates Stadium.
However, former Wolverhampton Wanderers man Leo Bonatini will likely begin the game on the substitutes' bench.
Vitoria de Guimaraes possible starting lineup: Douglas; Rochinha, Tapsoda, Henrique, Hanin; Evangelista, Agu, Teixeira; Edwards, Duarte, Pereira
Arsenal possible starting lineup: Martinez; Bellerin, Holding, Mustafi, Kolasinac; Xhaka, Willock; Maitland-Niles, Smith Rowe, Pepe; Martinelli
We say: Vitoria de Guimaraes 1-3 Arsenal
While Emery will make alterations for this contest, we feel that Arsenal should still come through with minimal fuss. Vitoria showed their quality in the reverse fixture, which should result in the visitors possessing no complacency ahead of this game.