Pochettino and sporting director Ramon Planes have left Espanyol with the club bottom of the Primera Division table following a miserable run of results.
A statement on the club's website on Monday night said that both men had left the club following consideration by the board.
"This afternoon, the club and the coach agreed to terminate by mutual consent the contract that united them," the statement said.
"Ramon Planes has ceased his duties as sporting director of the club, having also reached an agreement for termination by mutual agreement.
"RCD Espanyol wishes to publicly thank the dedication and commitment of both professionals during their time with the club and wish them every success, both personally and professionally."