His position will be taken by the man he replaced, Middlesex director of cricket John Emburey.
In a statement, Middlesex, the Lord's-based side, said: "Due to personal reasons, Richard Pybus has asked to be released from his contract as first team coach with immediate effect. The club has agreed to this request. John Emburey, director of cricket, will assume first team coaching duties."
Former England off-spinner Emburey was recently shortlisted for the still vacant post of India coach but lost out to Graham Ford, previously coach of South Africa but now in charge of English county Kent, who eventually turned the job down.
Pybus, who only joined Middlesex in April from South African side Titans, with whom he won the Provincial Championship, has not enjoyed much in the way of success at Lord's.
Middlesex have not gone beyond mid-table in the County Championship First Division and didn't qualify for either the knockout stages of the 50-over Friends Provident Trophy or the Twenty20 Cup.