Zinedine Zidane's side head to the Etihad Stadium for Friday's last-16 second leg trailing 2-1 from the reverse fixture at the Santiago Bernabeu.
"I think when Zidane came [back], he got that chemistry back in place and after corona, I think Madrid came out solid, when Barcelona came out a bit segregated," he told Stats Perform News.
"Ramos and Benzema have been key, key players but, as I said, the whole team has shown a pretty solid shape.
"If you look at them without the results they have now, they are considered definitely [among] the favorites, Manchester City as well - these are two top teams in the world.
"It's going to be tough to go there and turn it around, but nothing is impossible in that sense. But also, Manchester City need to make up for the average season, if you can call it that.
"They can do it, but it's tough."
Barcelona, meanwhile, will need to improve their performance to overcome Napoli and reach the quarter-finals, after a 1-1 draw in Italy.
Much is expected of midfielder Frenkie de Jong, a €75million signing from Ajax last year who has yet to find his feet fully in Spain.
"He's a great player, a great talent and we hope to see much more from him over the coming years," said Seedorf.
"It's not easy to come to a new country and new club and perform. Barcelona... it's a privilege to come to a team that knows themselves so well, and you come into the same type of system.
"Frenkie will become better and better hopefully over the next years and we can enjoy his talent on the international pitches."
Similarly, Seedorf thinks new Chelsea signing Hakim Ziyech could find it tough to adapt to life in a new league - although he believes head coach Frank Lampard is the right man to help.
"Lampard has shown to have had a good, positive impact on the team and young players," Seedorf said. "Ziyech is a talent that will face challenges, because this is not the Ajax style of play, the Dutch style of play, and that's going to be his biggest challenge, I think: to adapt to a new style of play and everything that comes with it.
"But he has a proper mentor in place to guide him to the Premier League style and competitiveness that is needed. I think the ingredients are there for him to continue to spread his talent on the pitch and show that this next level was the right thing to do."