Science Programs within ORO are performed at the Oak Ridge National Laboratory (ORNL) and Oak Ridge Institute for Science and Education (ORISE), and Thomas Jefferson National Accelerator Facility (Jefferson Lab). At ORNL, researchers focus on basic and applied research to advance the nation's energy resources, environmental quality, scientific knowledge, and contribute to science education and national economic competitiveness. The Laboratory also performs work for non-DOE sponsors when such activities complement DOE missions and address important national or international issues. ORNL is operated by UT-Battelle LLC. ORISE is managed for DOE by the Oak Ridge Associated Universities, a not-for-profit consortium of 99 colleges and universities.

ORISE is a national leader in science education and research. Its focus is three core areas in support of DOE including: worker/public health and independent verification of environmental cleanup; weapons of mass destruction, national preparedness and emergency response; and science education, workforce development, and scientific review programs.

Jefferson Lab accelerates electrons for use as a probe to study the structure of matter. Jefferson Lab is operated by Jefferson Science Associates LLC. Additionally, Oak Ridge supports 10 Science laboratories and facilities at DOE sites throughout the United States.