The St. Louis County Hospital was a public hospital located at 601 South Brentwood Boulevard in Clayton from 1931-1986. It was funded by a one million dollar bond issue passed by county voters in 1927, and the original building was designed by the architectural firm, Aegerter and Bailey. In July of 1931 the hospital opened under the leadership of Dr. Eugene A. Scharff, and it primarily served private, pay patients. By 1936 the hospital's policy changed to make taking care of indigent County residents their primary role. The County Health Department was also located on the campus.

From 1940 to 1943 a second building (Building II) was added to serve as a health center for both the Hospital and the Health Department. In 1946, the new building was the site of the first Polio treatment center in the St. Louis area.

In 1962 the third and final unit of the Hospital (Building III) was opened to treat mental patients and chronically ill people over 65 years of age.

By 1986, many of the functions of the Health Department had been moved to separate facilities, clinics had opened in various areas to better serve their communities, and the facilities at the hospital had become outdated. In June of 1986, inpatient care at the Hospital campus was discontinued.