Last time they made the trip to Ramon Sanchez-Pizjuan in 2007, former boss Arsene Wenger decided to select a youthful starting XI.
The Gunners had gone into the match unbeaten in all competitions, but slumped to a 3-1 defeat in Andalucia that ultimately cost them top spot in Group H.
Sevilla, as they will tonight, went into that match in 2007 as reigning Europa League winners – or Uefa Cup as it was then known.
Manuel Almunia was preferred to Jens Lehmann in goal, with academy graduate Justin Hoyte at right-back over Bacary Sagna.
Armand Traore was selected at left-back with Kolo Toure and Philippe Senderos in the middle.
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Hoyte, now 38, went on to play for Middlesbrough, Millwall, Dagenham and FC Cincinnati before calling it a day in 2019.
Traore, meanwhile, had an eclectic career that led him from Juventus to Cardiff – but he has not had a club since he was 30.
Former Invincible Gilberto Silva was at the base of midfield, alongside Denilson and Cesc Fabregas.
In attack Wenger fielded Eduardo, Emmanuel Eboue and Nicklas Bendtner.
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Eduardo fired Arsenal into the lead on 11 minutes, but Arsenal were pegged back by future Barcelona star Seydou Keita.
Brazil striker Luis Fabiano gave Sevilla the lead on 34 minutes for a side that also boasted the likes of Dani Alves.
Wenger turned to Tomas Rosicky, Sagna and Theo Walcott from his bench.
But a penalty by former Tottenham striker Frederic Kanoute sealed the points on 89 minutes.
After falling to second in the group, Arsenal drew holders AC Milan in the round of 16.
They beat Milan 2-0 on aggregate, but went on to lose 5-3 across two legs to Prem rivals Liverpool.