A comfortable 2-0 loss at Butarque left Espanyol bottom of the table, five points adrift of safety approaching the midway point of the season.
In a statement released on Monday, the club said: "Espanyol reports that Pablo Machin has been relieved of his responsibilities as head coach of the men's first team.
"The club has made the decision as a result of the first team's sporting performance and with the clear intention of changing the team's situation in LaLiga."
"Coaches Jordi Guerrero, Jordi Balcells and Carles Martinez have also left.
"Espanyol thanks Pablo Machin and his technical staff for their application during these months of work and wishes them every personal and professional success."
Machin was appointed in October to replace David Gallego but managed just one win in 10 league games, although he did lead them to the last 32 of the Europa League, where they will face Premier League side Wolves.
Their first match of the new year will be the derby with Barcelona on 4 January.