Barcelona are top of Group D after winning their opening two matches against Sporting Lisbon and Juventus.
However, how Barca's fans will react to a tumultuous few weeks of political tension in Catalonia is less predictable with the support split like the rest of society in the wealthy northeastern region of Spain.
Pique, thinking he had doubled Barca's lead, initially celebrated but the referee and the official behind the goal correctly came to the conclusion that the defender had purposefully used his hand and disallowed the goal.
Valverde has overseen a sublime start of 10 wins to go with a draw at Atletico Madrid last weekend in his first 11 La Liga and Champions League matches in charge.
"FC Barcelona will display a 45x46 metre banner at Camp Nou before kick-off Wednesday night emblazoned with the phrase "Dialogue, Respect, and Sport" to call attention to the current situation in Catalonia", Barca said in a statement on Tuesday.
Barca's singing section also held up a banner reading "Freedom for Catalonia", whilst there were habitual chants in favour of independence in the 17th minute to mark the fall of Catalonia in the Spanish War of Succession in 1714.
The good news for Barcelona is that they did not miss a beat despite being down a man, and were up 3-0 by the 65th minute of the contest, with Lionel Messi scoring his 100th Champions League goal.
"It was a great game, in a great atmosphere, in a great stadium", said Valverde.
The Champions League game against the Greek side was the first at the Nou Camp since the La Liga clash with Las Palmas on October 1 which was played behind closed doors in what the club said was a protest at police crackdowns on the banned referendum on independence in the region that day.
And for Messi, Valverde added: "Messi distributes the game and looks on the field for players with whom he can connect".