Valencia fired Marcelino Garcia Toral on Wednesday, three matches into the league campaign, making him the first La Liga coach to be dismissed this season.
Valencia have won one match, lost one and drawn another so far this term and sit 10th in the table and face Barcelona away on Saturday.
They won their last match before the international break, 2-0, at home to Mallorca.
"Valencia CF has communicated this Wednesday to Marcelino Garcia Toral the termination of his role as coach of the first team," said the Mestalla outfit in a brief statement.
"The club would like to thank him for his work and dedication during his time with our club and wish him the greatest success for the future."
Marcelino took over in May 2017 and led the club to fourth-place finishes in his two seasons in charge as well as to victory in the Spanish Cup last season.
The club did not name a replacement, although local media reported their choice was Albert Celades, former boss of Spain's under-16 and under-18 teams and assistant to Julen Lopetegui in his brief time as coach of Real Madrid.