Roma begin their Champions League campaign against the trophy holders and rely on Edin Dzeko, Cengiz Under and debutant Nicolò Zaniolo.
It kicks off at the Bernabeu at 20.00 UK time (19.00 GMT) in the same group as Viktoria Plzen and CSKA Moscow.
The Giallorossi were the surprise outfit of the tournament last season, topping the group ahead of Chelsea and Atletico Madrid, knocking out Barcelona and reaching the semi-finals.
Many of those players have since left and Coach Eusebio Di Francesco is having some teething problems in Serie A with one win, two draws and a defeat.
Javier Pastore is out injured, so Di Francesco takes a huge gamble and throws Italy Under-21 international Nicolò Zaniolo in from the start.
He arrived from Inter’s youth academy as part of the Radja Nainggolan transfer and has never played a single Serie A game, yet was called up by Roberto Mancini for Nations League matches against Poland and Portugal earlier this month.
Zaniolo follows in the footsteps of Daniele De Rossi by making his debut in the Champions League before Serie A and he only turned 19 in July.
Cengiz Under and El Shaarawy get the nod to support Dzeko, although Justin Kluivert isn't even on the bench.
Real Madrid became the first side to win the Champions League for three years in a row, but Coach Zinedine Zidane has left along with Cristiano Ronaldo.
This is the first time Real Madrid have started a Champions League match without Cristiano Ronaldo since March 10, 2009, a 4-0 defeat at Liverpool.
They are a different beast under ex-Spain boss Julen Lopetegui, but return to the 4-3-3 formation after a few games as 4-2-3-1.
Thibaut Courtois was a big expense over the summer, yet Keylor Navas takes the gloves, with Isco chosen in midfield rather than Marco Asensio to complete the attack with Gareth Bale and Karim Benzema.
These clubs have met 10 times before with six Spanish wins, three for the Romans and only one draw.
Their record at the Bernabeu is perfectly even, a draw and two wins apiece, the most recent Giallorossi victory taking them to the quarter-finals in 2008.
Real Madrid: Navas; Carvajal, Varane, Ramos, Marcelo; Casemiro, Kroos, Modric; Bale, Benzema, Isco
Real Madrid bench: Courtois, Nacho, Mariano Diaz, Lucas Vazquez, Llorente, Asensio, Ceballos
Roma: Olsen; Florenzi, Manolas, Fazio, Kolarov; Nzonzi, De Rossi, Zaniolo; Under, Dzeko, El Shaarawy
Roma bench: Mirante, Marcano, Santon, Cristante, Lorenzo Pellegrini, Perotti, Schick
Ref: Kuipers (NED)