The incident happened at a house in Dan Corkery Place, Macroom, just before 2am.
It is understood that Gardai were called to the house, where they found a man in his 40s with stab wounds. He was pronounced dead at the scene.
A man and a woman also in their 40s were taken to hospital with non life-threatening injuries.
Gardai are asking anyone with information to contact Macroom Garda Station on 026 20590, The Garda Confidential Telephone Line on 1800 666 111, or any Garda Station.