Ronaldo strikes twice as Real close on Atletico
Sergio Ramos and Daniel Carvajal also netted for Real who are second on 82 points, three behind Atletico before their trip to Valencia on Sunday with both teams having played 34 games.
Barcelona, mourning the death of former coach Tito Vilanova on Friday, are now in third place with 81 points from 34 matches and travel to Villarreal on Sunday.
Real did not risk Gareth Bale or Karim Benzema against Osasuna ahead of their Champions league semi-final second leg at Bayern Munich on Tuesday in which they hold a 1-0 advantage.
But there was no holding Ronaldo, who only returned from injury in Wednesday's first leg against Bayern at the Bernabeu having been out since early April, as he cut in from the left wing and fired into the corner of the net after six minutes.
The prolific Portuguese forward then cracked home a fine long-range drive after 52 minutes before being substituted leaving Ramos and Carvajal to wrap up the win with headers.
"Cristiano is fine and he played with more assuredness and confidence than on Wednesday. It all went well for him and us," Real coach Carlo Ancelotti told a news conference.
"We were able to rest some players and it was a good game even though there was no great intensity."
The Italian added that Bale and Benzema will be fine to face Bayern, saying: "Benzema is improving and won't have any problems for Tuesday. He will train normally tomorrow.
"Bale had a cold that has left him very weak and we have preferred that he trains on his own but he will also be ready to play," he said.
Earlier, Getafe beat Malaga 1-0 to boost their survival hopes and confirm the relegation of Real Betis who host Real Sociedad later today.
Osasuna went out with the aim of being solid and frustrating Real as they did at home in the league, where they got a point, but Ronaldo only needed a sniff of goal which fullback Damia Abella gave him after a few minutes and he was unforgiving.
Real controlled the midfield with Osasuna limited to counter-attacks where they created little danger.
There were anxious glances when Ronaldo held the back of his leg midway through the first half but it proved a false alarm and he continued to look lively on the ball.
A free-kick from the Portuguese forward whistled just wide and from another set-play he set up Ramos who shot over.
Marcelo and Luka Modric also tested keeper Andres Fernandez and after the restart Ronaldo extended the lead with a moment of quality when his shot from distance nestled in the top corner.
Shortly afterwards he was taken off but the goals continued to flow as Ramos nodded in an Angel Di Maria cross and then Isco set up substitute Carvajal to head in for a resounding victory.