Madrid welcome Celta Vigo to the Bernabeu on Saturday with several players definitely missing, including full-backs Marcelo, Fabio Coentrao and Alvaro Arbeloa, and question marks against a number of others.
According to reports in Spain, up to seven Madrid players have returned from international duty with knocks, and with a testing Champions League trip to Borussia Dortmund coming up next Wednesday, coach Jose Mourinho will be loathe to take any risks against Celta.
However, Madrid captain Casillas believes the Spanish champions can deal with the injury situation, saying on his club's website: "We have sufficient options to cover for the absentees. There are also very capable players in the reserves.
"I'm sure the boss will pick the best people for the game against Celta."
Madrid remained eight points adrift of Primera Division leaders Barcelona after drawing 2-2 with their arch rivals at the Nou Camp just prior to the international break.
Barca go to Deportivo La Coruna this weekend looking to keep that gap intact, although any slip up by Tito Vilanova's men could see in-form Atletico Madrid take over at the summit.
Atletico joined Barca on 19 points after beating fellow high-flyers Malaga 2-1 last time out for their ninth successive win in all competitions.
The Rojiblancos go to mid-table Real Sociedad this weekend with coach Diego Simeone expecting a testing match, despite his side winning 4-0 at the Anoeta last season.
"We're looking at it as a difficult and tough match and we'll need to be at our best against opponents who are improving a lot at home," said Simeone.
Sociedad have won all three of their home league matches this season, but have lost all four on their travels.
Barca and Atletico boast a five-point advantage over third-placed Malaga, who will be looking to bounce back from their first loss of the campaign when they host Real Valladolid.
Like a number of their rivals at the summit, Malaga have a big European date coming up next week with the visit of AC Milan in the Champions League.
Malaga midfielder Ignacio Camacho knows his side can ill afford to be distracted by that game, though, saying of the Valladolid match: "I think it'll be a difficult game. We need to focus on winning this home match, as it's important we don't lose these three points which could prove crucial at the end fo the season."
Valencia, who travel to BATE Borisov next week, are at home to Athletic Bilbao on Saturday in a match between two sides who have under-performed at the start of the Primera Division season.
On Sunday, rock-bottom Espanyol face Rayo Vallecano, second-bottom Osasuna welcome fourth-placed Real Betis, Levante go to Getafe and Granada meet Real Zaragoza.
In Monday's late match, seventh-placed Sevilla and sixth-placed Real Mallorca will both be looking to recover from back-to-back league defeats when they meet at the Ramon Sanchez Pizjuan.
Chelsea won the Europa League on Wednesday. The Blues defeated Benfica 2-1 on injury time goal from Ivanovic.
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