The facility was established as a fever hospital by the trustees of Manchester Royal Infirmary, largely because of the insistence of John Leigh, the first Medical Officer of Health for Manchester; it opened as the Barnes House of Recovery and Convalescent Home for Fever Patients in 1871.

[3] The hospital was sold to Manchester City Council in 1895 for £4,900.

The council agreed to receive and treat any patients with infectious diseases, including Erysipelas, and for the first four years it was agreed that the medical staff of the infirmary could instruct students in the fever wards.

[5] In September 1985, the first person with HIV/AIDS to be detained to hospital under the Public Health (Control of Disease) Act 1984, was detained at Monsall Hospital.

[6] This led to major protests and he was allowed to leave after 10 days in hospital.