Having crashed out of the FA Cup following a 2-1 quarter-final defeat to Watford at the weekend and with Leicester now 11 points clear of the Gunners in the Barclays Premier League, Arsene Wenger's side are staring down the barrel of a trophyless season.
But is there any hope of overturning the 2-0 home defeat in the first leg? Here, Press Association Sport takes a look at five major talking points ahead of the contest.
CAN ARSENAL ACHIEVE MISSION IMPOSSIBLE?
Improbably.
Wenger said after the FA Cup defeat to Watford that his side now need to "make the impossible, possible" at the Nou Camp - but Barcelona's record in front of their own fans is utterly formidable.
Arsenal have not made it past this stage of the Champions League since reaching the quarter-finals six years ago and, while Wenger's job of continually qualifying for the tournament - and subsequently getting out of the group stages - this looks like another time where the round of 16 will see the Gunners go.
WILL BARCA TAKE IT SERIOUSLY?
Luis Enrique has certainly insisted it is business as usual.
The Barca coach could have looked to make a few changes - maybe rest Lionel Messi or Luis Suarez to give Arsenal a sporting chance - but he has said he and his players will treat the game with the respect it deserves.
Wanting to extend a record of 37 games unbeaten will also spur on the home side, "37 games without losing is astonishing, and we want to extend it further" - skipper Andres Iniesta said after the 6-0 thrashing of Getafe at the weekend.
SO WHAT ABOUT WENGER?
The Frenchman may feel he is in a lose/lose situation here.
He could, and most likely will, go full strength in the hope his star players can pull off a major upset - but can he risk losing further players to injury?
Alexis Sanchez and Mesut Ozil were recalled against Watford and could not inspire a victory so if one were to take a knock in Catalonia, would it be seen as a derailment of the faint hopes the club have of winning the Premier League?
WHO COULD PROVE TO BE AN UNLIKELY ARSENAL HERO?
Virtuoso performances have been hard to come by at the Emirates Stadium since the turn of the year, with even the best of Arsenal's players struggling for form, fitness or both.
Goals have been at a premium as Olivier Giroud and Theo Walcott endure struggles, the FA Cup replay against Hull aside, while Sanchez has not looked the same since returning from a hamstring injury.
The Chile international will want to impress against his former club, however, and Ozil always has the ability to conjure up something out of nothing - Danny Welbeck has also looked sharper than many of his team-mates and could be vital to Arsenal's slim chances of progressing.
ARE ALL OF ARSENAL'S PROBLEMS IN ATTACK?
Sadly not.
Per Mertesacker may have said his attacking colleagues are lacking a "killer instinct" in front of goal - but the German World Cup winner and his fellow defenders must shoulder their portion of the blame for recent results.
Both Watford goals shone a light on defensive frailties, while David Ospina will never be deemed as safe a pair of hands as the injured Petr Cech.
Arsenal did well to nullify the threat of Messi, Suarez and Neymar in the home leg - for 70 minutes at least
Then they caved with errors at the back costing them dear, mistakes which simply cannot be repeated on Wednesday night.
Source : PA
Source: PA