Manchester United have confirmed their defender has fractured his arm and will undergo a surgery on 29 October, which has forced him to miss the clash against Burnley at Old Trafford on Saturday.
The Ecuadorian international picked up the injury during the Red Devils' 1-0 win over Manchester City in the fourth round of the EFL Cup during the midweek. Despite that, he completed the entire match as Jose Mourinho saw his side progress further in the competition.
Valencia is set to join summer signing Eric Bailly on the sidelines. The former Villarreal central defender suffered a knee injury in the 52nd minute during the league defeat against Chelsea on 23 October.
Bailly will be joined the former Wigan Athletic man in the treatment room, while Chris Smalling has also failed to make it to the squad to face Sean Dyche's side as he is still recovering from his injury.
"Antonio is having surgery today. He has a fracture in his arm. With Michael Carrick, the decision was to play with only two midfield players and also thinking about the next match against Fenerbahce [on Thursday]," Mourinho told United's official website.
"The problem for us is having injuries all in the same area with [Eric] Bailly], Chris [Smalling] and Valencia. They were the three players that start almost every match in the Premier League and now we have lost all three in the same period."
The situation has forced the former Real Madrid and Chelsea to field Matteo Darmian in the right-back position, while Daley Blind and Marcos Rojo continue as the two central defenders against Burnley. Mourinho claims it is an opportunity for both Rojo and Darmian to impress in the absence of injured defenders.
"But that's football and it's an opportunity for others to play. We trust Darmian and we trust Marcos Rojo to have a positive influence," United manager added.