The former Iran national football team and Bayern Munich midfielder took charge of the Rasht-based football team last season and purchased the shares of the club at the start of the new Iran Professional League (IPL) season.
Karimi has resigned following poor results in IPL.
Ali Nazarmohammadi and Nader Dastneshan have been nominated to replace Karimi in Sepidrood.
Under guidance of Nazarmohammadi, Sepidrood won promotion to the IPL in May 2017.
Sepidrood will continue its fight out of the relegation zone when the team hosts rock-bottom Esteghlal Khuzestan on Friday.