Real's legendary number one Iker Casillas will miss Wednesday's Champions League match after suffering a fracture in his left hand and De Gea admitted it's a significant piece of team news when asked about it at United's pre-match press conference.
"Every time Iker Casillas is not there, he is a great loss," said De Gea, a former servant of Real's local rivals Atletico Madrid.
"It is a great loss because he is the captain of Real Madrid and Spain. But Real have two other keepers who can play as well as Casillas does."
When Casillas came off with the injury, early in last month's Copa del Rey match at Valencia, he was replaced by substitute keeper Antonio Adan. But Jose Mourinho has since signed the more experienced Diego Lopez, who began his career at Real and was in goal when Los Blancos beat Sevilla 4-1 at the weekend.
David De Gea - Manchester United
Born: 7 November 1990, Madrid, Spain
Joined United: 1 July 2011
Debut: 7 Aug 2011 v Man City
Former clubs: Atletico Madrid
International: Spain U-23s (Olympics)
Iker Casillas - Real Madrid
Born: 20 May 1981, Mostoles, Spain
Joined Real: 1990 as a youth player
Debut: 12 Dec 1999 v Athletic Bilbao
Former clubs: None
International: Spain (143 appearances)