After the 2-0 defeat at the Etihad Stadium last month, City know winning at Camp Nou will be difficult but both Samir Nasri and Joe Hart are optimistic about their chances.
Barca have lost two of the following three league matches since that win and Nasri believes they can take heart from the latest defeat to Real Valladolid on Sunday.
"I think anything is possible in football," the France international told reporters. "I saw them this week against Valladolid. It just shows they are human.
"They are a great team but we are not going to have any problem to respect them because we know it is a great team. We have to do everything from the start.
"We have nothing to lose. If you go there and you lose it is no more, but if you get a result it will be fantastic. I think we have nothing to lose. Just attack them from the start and try to score an early goal."
Hart echoed the comments of his team-mate and insisted City must summon the early-season form that saw them beat Bayern Munich in the Allianz Arena.
"The tie is not over and we'll go into the game remembering what we've done this season and what we are capable of and I think that’s how we have to look at it," Hart told the club's official website.
"A positive performance is key and a result would be fantastic, but we need to go out there and show we can really play against the likes of Barcelona.
"We've shown what we can do when we beat Bayern Munich away in December and while it's going to be tough, it's not impossible.
"I felt we were there in the first leg, had sized them up and were ready to go, but stuff happens in big games and if you give a predator like Barcelona a sniff of blood and unfortunately that's what happens."
