Simon Flexner (March 25, 1863 - May 2, 1946) was a physician, administrator, and professor of pathology at the University of Pennsylvania. He was the first director of the Rockefeller Institute for Medical Research (1901-1935) and a trustee of the Rockefeller Foundation. He was also a friend and advisor to John D. Rockefeller, Jr..

He was the elder brother of Abraham Flexner.