The 18-year-old Argentine, who joined from River Plate in the summer for a reported 45 million euros fee, has impressed since arriving at the Bernabeu. He has featured 12 times in all competitions this season (nine in La Liga and three in the Champions League), scoring once but yet to register an assist.
However, the midfielder has been sidelined after being diagnosed with pubalgia, a groin injury that will keep him out for an indeterminate period.
A statement from Real Madrid read: "Following tests carried out today on our player Franco Mastantuono by the Real Madrid Medical Services, he has been diagnosed with pubalgia. His recovery will be monitored."
Mastantuono's absence adds to Real Madrid's growing injury list, with Antonio Rudiger, David Alaba, and Dani Carvajal all unavailable for the Anfield showdown.
Alaba remains sidelined with a muscle injury (expected return mid-November), Rudiger is still recovering from a hamstring problem (mid-November), and Carvajal continues his rehabilitation after knee surgery (early January 2026).
Head coach Xabi Alonso confirmed that Trent Alexander-Arnold, who recently returned to fitness after a hamstring issue, is available but short of match sharpness. "Trent is perfectly fine. He didn't play against Valencia due to tactical reasons, but he's ready. We need him; he has tremendous quality, he's in a new phase of his career, and we have to help him perform at his best," Alonso said.
Federico Valverde is expected to start at right-back, with Alexander-Arnold likely to begin on the bench due to his lack of recent minutes.
For Alonso, Tuesday night marks an emotional return to Anfield. The Spaniard enjoyed a five-year spell at Liverpool from 2004 to 2009, winning the Champions League in 2005.
"Back to Anfield? I'm trying not to let my emotions cloud my judgment. I want to focus on the match. It always feels good to return to a place where you have been loved so much," he said.
Real Madrid have made a strong start to their European campaign, winning all three of their league-phase matches to sit on nine points. They will aim to maintain that perfect record when they face Liverpool under the Anfield lights on Tuesday night.
Mikel Arteta has admitted Arsenal must remain grounded despite their stunning start to the season, as the Gunners continue to battle on multiple fronts at home and in Europe.
Brazil coach Carlo Ancelotti has played down Vinicius Junior's angry reaction to being substituted in Real Madrid's 2-1 Clasico win over Barcelona, confirming that the forward admitted his mistake and apologised.
Tottenham manager Thomas Frank has eased fears over injuries to Mohammed Kudus and Djed Spence ahead of Tuesday's crucial Champions League clash with Copenhagen.
Bayern Munich defender Hiroki Ito has returned to full training following a metatarsal fracture sustained earlier in the season.
