The race will be her 86th marathon, her spokesman Bruce Pfaff said. "She's a ball of energy," he said. "Running helps her focus."
The Republican even squeezed a marathon into her schedule the same day she voted on the health care reform bill. "A staff person met her at the finish to take her to vote and then she showered," he said.
Schmidt has run as many five marathons a year, typically logging 6 miles a day before going to work. On trips overseas, including to Afghanistan, she's run with military personnel, said Pfaff.
In the midterm elections November 2, Schmidt is running against Democrat Surya Yalamanchili - who said he is not running the marathon.
The marathon begins in Arlington, Virginia, and winds into Washington, passing the Jefferson Memorial and the National Mall and numerous monuments. It ends at the Marine Corps National War Memorial.
Registered runners include a variety of Capitol Hill workers, said race spokeswoman Tami Faram.
Celebrity chef Art Smith, a favorite of Oprah, is also slated to compete. Mexican runner Ruben Garcia Gomez is expected to do well - likely finishing in around 2 hours and 22 minutes, and the returning women's champion, Muliye Gurme of Ethiopia, is predicted to finish in about 2 hours and 40 minutes.