However, Slavia play host to the La Liga champions aware that victory will move them level on points with Ernesto Valverde's side in Group F.
There have been times this season when Ernesto Valverde would have feared for his job at Camp Nou, especially when Lionel Messi was struggling to shake off fitness issues which began in the summer.
However, five successive wins in all competitions have silenced the majority of talk regarding the manager's future, with Barca now sitting at the top of the La Liga standings.
Valverde's main objective will now be to ensure that his squad build on their recent dominant wins over Sevilla and Eibar, aware that Slavia are capable of defeating any opponents on their own patch.
Nevertheless, Messi's break from the team will only have increased the desire of the Argentine to maintain his tag as the best player in the world, something he will feel that he has justified with his recent return of two goals and three assists from four outings.
Barcelona still have plenty of work to do in order to make the last 16, however, and it may take more brilliance from Messi to get the better of a solid Slavia outfit.
On the back of last season's run through to the Europa League quarter-finals, Slavia earned a draw away at Inter Milan in their opening fixture and pushed Borussia Dortmund all of the way at the Sinobo Stadium on matchday two.
While picking up just one point from those games has left Slavia struggling to achieve a top-two position, Jindrich Trpisovsky will reiterate to his squad that they can throw everything at Barcelona on Wednesday night with no pressure on their shoulders.
This week's fixture is arguably one of the biggest in Slavia's history, having never previously squared off against Barca or Real Madrid in a competitive encounter.
Slavia Prague form: WWWLWW
Barcelona form: LWWWWW
With this weekend's El Clasico fixture being cancelled, Valverde will feel that he can name a full-strength starting lineup.
Slavia under-performed at the weekend, with a second-half comeback being required to record a 3-1 victory over Pribram.
Slavia Prague possible starting lineup: Kolar; Coufal, Kudela, Hovorka, Boril; Sevcik, Soucek; Masopust, Stanicu, Olayinka; Teci
Barcelona possible starting lineup: Ter Stegen; Semedo, Pique, Lenglet, Alba; Arthur, Busquets, De Jong; Messi, Suarez, Griezmann
We say: Slavia Prague 1-3 Barcelona
While Slavia have already shown that they can rise to the occasion against some of the top clubs in Europe, we expect a rejuvenated Barca to register a comfortable win on Wednesday night, having overcome their previous inconsistent run of form.