Santiago Solari insisted his decision to leave Isco as an unused substitute in a 2-1 win at Betis was nothing personal against the Real Madrid midfielder.
Isco was benched despite Solari being without Gareth Bale, Lucas Vazquez, Toni Kroos, Marco Asensio and Marcos Llorente for Sunday's visit to the Benito Villamarin.
And even when striker Karim Benzema had to be substituted at half-time due to a fractured finger, Solari instead gave a Liga debut to B team striker Cristo Gonzalez.
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Dani Ceballos and Brahim Diaz, also making his league debut, were then introduced after Sergio Canales struck to cancel out Luka Modric's early opener.