Keylor Navas and Isco start for Real Madrid against Roma, while Valencia take on Cristiano Ronaldo’s Juventus without Geoffrey Kondogbia.
Julen Lopetegui appears to be rotating his goalkeepers as Keylor replaces Thibaut Courtois between the sticks, while Isco is preferred to Marco Asensio.
Roma, for their part, give a debut to teenage midfielder Nicolo Zaniolo, who partners former Sevilla man Steven Nzonzi in the middle of the park.
Elsewhere, Kondogbia joins Ezequiel Garay on the treatment table for Valencia, but Jeison Murillo makes his long-awaited return in defence.
Los Che are also the first Spanish side Ronaldo will face competitively since leaving Madrid over the summer.
The capital giants beat Roma in the International Champions Cup last month and knocked them out of the Champions League two years ago, although the Giallorossi did stun Barcelona to reach the semi-finals earlier this year.
Conversely, this is the first official meeting between Valencia and the Italian champions.
Real Madrid: Keylor; Carvajal, Varane, Ramos, Marcelo; Modric, Casemiro, Kroos; Bale, Benzema, Isco
Roma: Olsen; Florenzi, Manolas, Fazio, Kolarov; Zaniolo, Nzonzi, De Rossi; El Shaarawy, Dzeko, Cengiz
Referee: Brych (GER)
Valencia: Neto; Vezo, Murillo, Gabriel, Gaya; Soler, Parejo, Wass, Guedes; Rodrigo, Batshuayi
Juventus: Szczesny; Cancelo, Bonucci, Chiellini, Alex Sandro; Khedira, Pjanic, Matuidi; Bernardeschi, Mandzukic, Ronaldo
Referee: Kuipers (NED)