The Spaniard has reiterated his defender's importance to the club's cause, with several key members rested for their weekend fixture
Team-mates Sergio Ramos and Raphael Varane have been preferred at the heart of los Blancos' defence recently, but fixture congestion has prompted their exclusion from the latest squad as trainer Jose Mourinho offers them a break.
But Karanka confirmed his faith in Pepe, telling reporters: "Pepe is an extremely important player for us, both now and for the future.
"If there is anyone who has helped Varane to become what he is, then that person has been Pepe.
"Some players such as Varane, Ramos and [Fabio] Coentrao have played three matches in a row and deserve to rest," the 39-year-old added.
"We've always selected teams in order to win the matches, and I'm sure tomorrow's line-up will be very strong in order to win the game. The coach will select the players in the best conditions."
Captain Iker Casillas has remained sidelined as Diego Lopez continues his fine form between the posts after arriving in January, and Karanka maintained the competition for the starting jersey proves the strength of the side.
"Lopez is here to contribute. Those of us who knew him are not surprised. He has played some great games. What the manager has done is play the man in the better form.
"Iker is on the road to recovery and we hope he's back as soon as possible. We have fantastic goalkeepers and that's good for the team."
Xabi Alonso and Cristiano Ronaldo are in a race to prove their fitness for the upcoming match, while Angel Di Maria will miss out after suffering a hamstring injury against Manchester United.