Madrid are due to face City at the Etihad Stadium on August 7.
But Mariano, 26, will be unavailable for selection by Zinedine Zidane after he tested positive for Coronavirus.
Madrid’s players returned to training on Tuesday, after being granted a little break following their LaLiga title win.
Following his positive test at Madrid’s training ground, Mariano must now self-isolate and will miss the trip to Manchester in 10 days’ time.
“After the COVID-19 tests carried out individually on our first football team yesterday by the Real Madrid Medical Services, our player Mariano has given a positive result.
“The player is in perfect health and complying with the sanitary isolation protocol at home,” an official club statement read.