Valencia held Barca to a 1-1 draw last season at the Mestalla while Sergio Busquets' last-gasp goal secured a 1-0 victory for Luis Enrique's side in the previous campaign.
Fallen La Liga giants Valencia, who were Spanish champions in 2002 and 2004, have endured another season of upheaval, and sacked coach Pako Ayesteran having lost their first four games.
New boss Cesare Prandelli, however, got off to a winning start last week at Sporting Gijon.
"We're facing an unknown Valencia side because of the short time Prandelli has been in charge, and defensive organisation and good positioning are his hallmarks," Luis Enrique told a news conference on Friday.
"Valencia's situation is not positive but the quality of their players means it can always be difficult for you.
"Playing away from home is always difficult and at Mestalla, with a vociferous support against you, it is even harder. I can't remember a single easy game there."
Barcelona thrashed their former manager Pep Guardiola's Manchester City 4-0 on Wednesday in the Champions League, but Luis Enrique has a shortage of options in defence for the trip to Valencia, with Sergi Roberto, Jordi Alba and Gerard Pique all injured.
The coach said he would happily play versatile midfielder and centre back Javier Mascherano at right back again after the Argentine's strong display against City. He also did not rule out calling up a player from the reserve side to his squad.
Barca have little to worry about in attack, with talisman Lionel Messi scoring a hat-trick against City.
Luis Enrique said he agreed with Prandelli's assessment that there was no formula to stop the five-times world player of the year.
"If Leo is on form it's very difficult to find a solution for him, we haven't seen anyone do it so far," he added.
The coach also said he was pleased that Brazilian forward Neymar signed a new contract with the club until 2021 on Friday.
"Neymar's new contract is great news. It shows that he is a top level player, that he has evolved and that he feels very comfortable at the club and with his team mates and is hungry to win more trophies."
(Reporting by Richard Martin; Editing by Toby Davis)
