Éder Militão suffered a torn ACL while Rodrygo and Lucas Vázquez were substituted in the first half of Real Madrid's 4-0 win over Osasuna on Saturday in a further compounding of injury woes.
Sources have told ESPN that Militão is expected to be out for nine months, while Rodrygo and Vázquez face three to four weeks out of action.
Vinícius Júnior scored a hat trick for Madrid and Jude Bellingham netted his first goal of the season, but the victory was soured by the triple injury blow to Militão, Rodrygo and Vázquez.
"It was a good game -- we controlled it well from the start," coach Carlo Ancelotti said in his postmatch news conference. "From when we opened the scoring, the team looked good. The shame is the injuries in the first half. We're assessing them now, and we'll see.
"Three injuries in the first half is quite strange. The calendar is demanding and doesn't allow the players to rest. They go into games tired, so the risk of injuries is higher."
Rodrygo -- who had just returned to the team after recovering from a hamstring problem -- was withdrawn in the 20th minute at the Bernabéu and replaced by Brahim Díaz.
Militão needed treatment 10 minutes later before being stretchered off, with youngster Raúl Asencio being introduced in his place.
Madrid confirmed in a statement later on Saturday that Militão has torn the ACL in his right knee and will undergo surgery in the next few days. The Brazil international missed a majority of last season with an ACL tear in his left knee. It is the fourth ACL injury suffered by a Madrid player in the past year, with Thibaut Courtois and David Alaba having also suffered tears.
Full-back Vázquez was then withdrawn at halftime and replaced by Luka Modric.
Madrid are short in defence, with Dani Carvajal out for the season with a serious injury and Alaba not yet fully recovered.
They are also without goalkeeper Courtois, who has a thigh injury, and midfielder Aurélien Tchouaméni -- who sometimes fills in at the back -- who has an ankle sprain.
"We have to thank the academy for the work they've done with [Asencio]," Ancelotti said. "He's a player we need at this time ... Raul has been doing well with [reserve team] Castilla and now he'll be with us."
Ancelotti would not say if the string of injuries made January signings more likely.
"We'll assess it in the coming months," he said. "Right now, there's nothing we can do. We'll evaluate what we can do in January."
"I don't want to talk about it because it hurts me to see my teammates crying," Diaz said postmatch when asked about the club's injury woes.
"It breaks my heart. I've come back from a long injury and now it's their turn. It seems like they could be longer than usual."
Madrid had gone into the Osasuna game under pressure, after being beaten twice at home in their previous two matches, against Barcelona and AC Milan.
They now have a two-week break before returning to action against Leganés on Nov. 24 and travelling to Anfield to play Liverpool in the Champions League on Nov. 27.
Saturday's win leaves Madrid six points behind LaLiga leaders Barcelona, who play on Sunday.