Santiago Canizares and David Albelda look to have played their last games for Valencia.
The duo were initially dropped by manager Ronald Koeman and told they would not play in the two matches before Christmas as the club looked to arrest an alarming slump in form.
But vice president Enrique Lucas has now revealed that Valencia have made "the necessary decision to get rid of Canizares and Albelda".
Club president Juan Soler has backed Koeman's decision with the duo now expected to exit the Mestalla.
Lucas, who admitted it was a "painful decision" said: "The president has accepted the coach's decision, understanding that every professional life has an end."
Valencia finished bottom of their UEFA Champions League group to crash out of Europe and are 13 points off the pace in seventh spot in the Primera Liga after a run of just one point from their last four matches.
Koeman had already admitted he was expecting to come in for some criticism over his decision to leave out the duo.
Speaking earlier in the week, he said: "There will be people that criticise me and people that agree with me, but I have to accept that and keep working."
The 38-year-old Canizares, capped 46 times by Spain, signed for Valencia in 1998 and is under contract until 2009.
And captain Albelda, who has 50 caps for the international side, was due to stay with the club until 2011.
Meanwhile, Miguel Angel Angulo's representative claims the striker is another player to be told he has no future under Koeman.
Jose Luis Tamargo told Radio Marca: "I was told today by the club's sporting director Miguel Angel Ruiz that Angulo will not be called up for the first team again this season.
"This comes as a real shock and although I respect the decision of the coach I do not understand it.
"Angulo does not plan to leave the club and he will wait and see what happens."