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Messi's future is uncertain beyond this summer, and Saturday's huge LaLiga clash between Spain's two biggest clubs in the capital may well be his last ever appearance in the greatest footballing rivalry on earth.
The Argentine talisman is in a front two with Barca coach Ronald Koeman opting for a 3-5-2 formation.
Gerard Pique and Sergi Roberto are doubts but make the squad, while Philipp Coutinho and Ansu Fati are both out due to injury.
As for Real, Zinedine Zidane is missing two key players in Sergio Ramos and Eden Hazard, with Dani Carvajal also absent.
Captain Ramos is still out with a calf problem, while Hazard - who has suffered an injury-plagued career at Madrid - did not recover from his most recent layoff in time to be included in the squad.
Real Madrid vs Barcelona confirmed lineups
Real Madrid XI: Courtois; Lucas Vazquez, Militao, Nacho, Mendy; Modric, Casemiro, Kroos; Valverde, Benzema, Vinicius
Barcelona XI: Ter Stegen; Mingueza, Aruajo, Lenglet; Dest, Busquets, Pedri, De Jong, Jordi Alba; Messi, Dembele