Ronaldo was named in the starting line-up for the fixture but returned to the dressing room soon after starting his pre-match exercises.
Manager Carlo Ancelotti instead put Isco in the starting line-up and the absence of Ronaldo is a huge concern for Real just seven days before the Champions League final with Atletico Madrid in Lisbon.
The Portugal captain limped out of the 1-1 draw at Real Valladolid on May 7 with an apparent thigh strain and missed last Sunday's 2-0 defeat at Celta Vigo that ended Real's chances of winning La Liga.
The Espanyol clash was meant to be his return to the starting line-up with Ancelotti saying during his press conference on Friday: "Cristiano Ronaldo is fine, available, and tomorrow he will play the match."
Ronaldo was hoping to start the match and score so he could win outright his third Golden Shoe for most league goals scored in a European league in a season.
Lionel Messi still has an outside chance of claiming a share of the award but would need a hat-trick in Barca's final clash with Atletico Madrid to draw level with Ronaldo and Suarez.
- Sports & Recreation
- Cristiano Ronaldo
- Carlo Ancelotti
- Atletico Madrid
- Real Valladolid