Speculation has suggested the Portuguese will miss the match at the Etihad Stadium through injury.
But Neville insists the 37-year-old’s profile and the style of play United will likely play against Pep Guardiola’s champions could mean his absence is not a significant blow to their chances.
Ronaldo is the team’s top scorer this season with 15 goals in 30 appearances across all competitions - but he has scored just one goal in his last 10 appearances for the Red Devils.
"Manchester United have been playing on the counter attack [at Manchester City in recent years],” Neville told Sky Sports.
“United over the last three or four years have been a counter-attacking team, punching out through Rashford and others on the break.
“Cristiano not being in the team, you'd never say it's a positive, but I don't see it as a big loss you might see it in other games.
“Because I think on the counter attack, Manchester United need to be dangerous today, and they're better off with Rashford up front than Cristiano.”