France's Ibrahima Konaté, the Real Madrid centre-back, suffered an injury to the lateral ligament of his right leg during the international break. Estimates suggest he could be sidelined for up to three weeks.
His participation against Villarreal is in serious doubt. The return date hinges on how his condition develops, and the club refuse to take any risks with his recovery.
Antonio Rüdiger is now the only first-team centre-back available to José Mourinho. Dean Huijsen must serve a suspension after his sending-off in the derby, Raúl Asencio recently went under the knife, and Militão is still completing his own recovery.
According to Sport, Mourinho is weighing up a move for Tchouaméni back into the heart of the defence, or a turn to academy players to complete the pairing.
The reserve side offers another route. Indeed, the Portuguese coach took in the derby against Atlético Madrid's reserves.
Mario Rivas is the standout name, the closest alternative after winning Mourinho's trust with a heavy load of minutes in pre-season.
Juan Martínez is another option the coach knows well, though his reduced role with the youth sides dents his chances of competing for the slot. Diego Aguado widens a list of candidates for a defence forced to improvise through sheer weight of absences.
Real Madrid's makeshift back line faces its first test against a Villarreal side that rediscovered their rhythm before the break. After a shaky start to the season, they beat Málaga and Levante in succession, scoring three goals in each.
That upturn came with Molero pulling the strings in the playmaker role, Ilias Akhomach handed a bigger part, and Ayoze Pérez as the attacking reference point. The formula clicked, and the Villarreal coach must now decide whether to stick with it at the Santiago Bernabéu.
All of this collides with Mourinho's obsession over the team's defensive balance. He used the break to iron out the imbalances laid bare during the derby against Atlético.
Testing that improvement with a patched-up defence is another matter, and he has little margin to make corrections mid-match. Villarreal kicks off a run of five games in 15 days, with Roma, Sevilla and Leipzig to follow before the Clásico.
That schedule demands Real Madrid rediscover the solidity that deserted them just as the absences returned to weaken the heart of their defence. Mourinho needs his emergency fix to protect and build on the work done over the break.
Dropping Tchouaméni into the centre would force the coach to rejig his midfield. Leaning on an academy player, meanwhile, means asking a youngster for an immediate answer in a fixture list that offers no rest.