The hospital, which was designed by Robert Clarke using a Corridor Plan layout, opened as the Oxford County Pauper Lunatic Asylum in August 1846.

[1] Littlemore railway station was opened, giving improved access to the hospital, in 1864, and two additional pavilion blocks connected by a recreation hall were completed to a design by Edwin Dolby and Henry Tollit in 1902.

[1] Dr Bertram Mandelbrote, who carried out pioneering work on creating therapeutic communities, became superintendent at the hospital in 1959.

[1] Some of the rear blocks were acquired by Yamanouchi (now Astellas Pharma) for use as a research facility [6] but then sold on, in 2008, to the SAE Institute for use as a training establishment.

[7] Meanwhile, a modern mental health facility known as the Littlemore Mental Health Centre,[8] which includes the Ashurst Psychiatric Intensive Care Unit (PICU) and Phoenix Ward (Adult Male in-patient), have been established on the opposite side of Sandford Road.