Real Madrid duo Eden Hazard and Casemiro have tested positive for coronavirus.
The La Liga champions said no other players of staff had recorded positive tests, as they travel to face Valencia on Sunday and could move top of the league if leaders Real Sociedad drop points earlier in the day.
The positive results would appear to rule Belgium's Hazard out of next Sunday's Nations League match against England while Brazil's Casemiro would be unlikely to be allowed to feature in upcoming World Cup Qualifiers against Venezuela and Uruguay.
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Real face Inter Milan in the Champions League later this month in what has become a crucial game in Group B, with German side Borussia Monchengladbach topping the table halfway through the group stage as Real sit third.
"Real Madrid CF announces that our players Casemiro and Hazard have given positive results in the COVID-19 tests carried out yesterday morning," read a statement on the club's website on Saturday.
"All the other players and the coaching staff of the first team, as well as all the club employees who work directly with them, gave negative results in that same test carried out yesterday.
"Likewise, it is confirmed again that all, with the exception of Casemiro and Hazard, have given negative results in the antigen tests carried out this morning."
Hazard, who moved to Madrid from Chelsea last year for a fee that could reach £130m, has missed most of the 2020/21 season so far through a muscle injury but started - and scored - in Real's 4-1 win over Huesca on October 31.
Hazard enjoyed a successful seven-year spell with Chelsea from 2012 to 2019, scoring 110 goals in 352 games, helping them win the Premier League and Europa League twice as well as the FA Cup and Carabao Cup once.
However, the 29-year-old - who is under contract until 2024 - has struggled with injury, fitness and form throughout his time at the Bernabeu, scoring just twice in 25 matches.
Speaking in the summer, he described his first season at Real as the worst of his professional career.
His goal against Huesca was his first in over a year in what was his first start of the campaign after he played his first minutes since July as a late substitute in a 2-2 draw at Monchengladbach on October 27.
Casemiro has featured in all seven of Real Madrid's La Liga fixtures so far this season, as well as their three Champions League games.
The 28-year-old defensive midfielder, who has 48 caps for Brazil, has made a total of 249 appearances for Real since making his debut in 2013.