The Serie A outfit slumped to their fourth defeat in five games, leaving them seven points clear of the relegation zone with six matches remaining.And controversial president Massimo Cellino, who is poised to complete his takeover of English Championship side Leeds United, has decided to pull the pin on Lopez's nine-month tenure.
Cellino had looked set to miss out on Leeds United having been found guilty of tax evasion but won his appeal against the English Football League over the weekend.
The Italian entrepreneur has overseen 36 managerial changes in two separate spells as president of Cagliari.
"The necessity to shake up the team in this final stage of the season to achieve the objective of safety made a change of management indispensible," read a Cagliari statement.
"This decision is very painful, as Lopez has proved himself as a professional and a man, and in the past as a symbol and captain of the squad.
"The club thanks the coach for his work and wishes him all the best for his future endeavours."
Lopez, who made 344 league appearances as a player for Cagliari before retiring in 2010, was appointed manager at the start of the season after serving as an assistant coach in 2012.
