The Roman Catholic Diocese of Issele-Uku (Latin: Isseleukuan(us)) is a diocese located in the city of Issele-Uku, Delta State in the ecclesiastical province of the Roman Catholic Archdiocese of Benin City, Edo State, Nigeria.

The diocese comprises six local government areas in the northern portion of Delta State.

The Diocese of Issele-Uku was created on July 5, 1973 from the territory which was once part of the Roman Catholic Archdiocese of Benin City.

It now covers the northern part of Delta State west of the River Niger and the state capital, Asaba including the following six Local Government Areas of Nigeria: Aniocha North and Aniocha South, Ika North East and Ika South, Oshimili North and Oshimili South, and has a land mass of 3,011 square Km.

The Diocese of Issele-Uku now covers six of the local government areas: Aniocha North and Aniocha South, Ika North East and Ika South, and Oshimili North and Oshimili South, and with a land mass of 3,011 square Km.