Los Blancos will be hoping to keep the pressure on Primera Division leader Atletico but are going up against a side that held them to a 2-2 draw in Pamplona in December.
After huge wins over Barcelona and Bayern Munich, Real Madrid's focus returns to La Liga's title race when Osasuna visits on Saturday.
Carlo Ancelotti's men are brimming with confidence after defeating Barca in the final of the Copa del Rey. That was swiftly followed by an excellent 1-0 triumph over reigning European champion Bayern in Wednesday's Champions League semifinal first leg at the Bernabeu.
Now the attention turns to the league and the club's attempt to overhaul rival Atletico, which currently tops La Liga and has a six-point cushion over third-place Madrid, albeit having played one game more.
With Osasuna struggling at the wrong end of the table, and the Blancos having won three straight league games in which they have scored 13 goals without reply, the signs point toward a comfortable home victory.
However, Madrid will need no reminding of the danger posed by Javi Gracia's men following a 2-2 draw in the reverse fixture in December, a game that saw the capital club come from two goals down and both teams finish with 10 men.
The hosts have superstar Cristiano Ronaldo available, after he made his return from a thigh injury in the triumph over Bayern. The forward is La Liga's top scorer with 28 goals and teammate Fabio Coentrao believes his availability further boosts Real.
"Any team would love to have Cristiano Ronaldo, the best player in the world," he told the club's official website. "It is a privilege to play with him and we made good combinations."
Osasuna's recent form can be best described as mixed. Gracia's charges are unbeaten in four, but have won just once in nine league matches.
With just four matches remaining, Osasuna is just three points above the drop zone and will be keen to pull off a shock in order to alleviate the threat of relegation.
Midfield duo Roberto Torres and Francisco Silva are suspended for Osasuna, while Madrid will continue to monitor the fitness of forward Gareth Bale, who has been struggling with illness.