United have had their worst start to a Premier League season since the inaugural edition in 1992/93 following back-to-back defeats to Brighton and Tottenham.
Chile face a pair of long-distance friendlies against Asian powerhouses on almost exactly the opposite side of the world.
Rueda said such a trip would be “exhausting” and that United “need him in a difficult moment” despite Chile’s matches in Sapporo on September 7 and Seoul four days later.
United’s 3-0 defeat at home to Spurs on Monday heaped the pressure on increasingly disgruntled manager Jose Mourinho and followed an abject performance in a 3-2 defeat on the south coast a week earlier.
It was the worst home defeat of Mourinho’s career as a coach.
Sanchez, 29, is his country’s record goalscorer (39 goals) and most capped player (121 appearances) and is known as “The Wonder Kid” back home.
He helped Chile win back-to-back Copa America titles in 2015 and 2016, both times beating Lionel Messi’s Argentina on penalties in the final.
While Sanchez sits out the arduous trips to the Far East, Barcelona midfielder Arturo Vidal will lead the team.
But Rueda has left out two star players — midfielder Jorge Valdivia and forward Esteban Paredes — from Chilean giants Colo-Colo as they have reached the Copa Libertadores quarter-finals for the first time in 24 years.
“It’s not up to me to think about what’s best for a club side, I’m interested in my team.
“But I know how exhausting the Copa Libertadores can be and this time I prefer those Colo-Colo players to concentrate on that.”
© Agence France-Presse