La Roja travel to Lisbon this week to face Portugal on Wednesday in the first meeting between the sides since the 2018 World Cup group stages.
Ronaldo scored a hat-trick, which included a stunning late free-kick, on that occasion to earn a 3-3 draw with Spain in Sochi.
Former Barcelona boss Luis Enrique has previously sided with Messi in the debate over who is the greatest modern player, describing the Blaugrana number 10 as the best in the world "in every position" and "the best in the history of football".
However, he has huge admiration for the way Juventus forward Ronaldo continues to strive for success at the age of 35 and after spending 18 years in senior football.
"Our goal doesn't change aside from the fact confronting a player of his profile can be motivational," he told reporters on Tuesday as he looked ahead to the friendly at Estadio Jose Alvalade.
"As a team, we will try to do things better than Portugal and try to cause them problems – that's the goal. Whether Ronaldo plays or not, the situation, the general approach to the game doesn't change.
"With regards to your other question, if you check through your newspaper archives, you already knew what my opinion is and I don't think it will be ideal for me again to comment on who is the best player in the world for me.
"What is worthy of praise is the fact that players like Cristiano and Leo Messi keep getting older but maintaining such a high level thanks to their professionalism, their ambition and their capacity to be motivated and keep achieving goals. Both Cristiano and Messi are examples of that."
Ronaldo has scored three goals and set up another in his first two Serie A appearances of 2020-21, with Juve beating Sampdoria 3-0 and then drawing 2-2 with Roma.
Messi has one goal in three LaLiga matches, with Barca beating Villarreal 4-0, Celta Vigo 3-0 and drawing 1-1 with Sevilla in Ronald Koeman's first three league games in charge.