Derbyshire Police said officers were called to an address in Canal Street, Ilkeston, on Wednesday night after reports of a disturbance.
A 48-year-old local man, who has not been named, was found injured inside the house and in spite of treatment by paramedics, he died.
A post-mortem examination revealed that he died from injuries suffered during an assault. A formal identification has not yet taken place.
A force spokesman said two men, aged 26 and 24, were arrested on suspicion of murder while a 26-year-old man and a 46-year-old woman were held on suspicion of conspiracy to commit murder.
The four remain in police custody and are being questioned.