While numerous politicians have called on Filner to step down, few have known him as long, or worked as closely with him on public issues, as Boxer.
"We’ve known each other for a long time, and have worked together on many issues that are important to the people of San Diego -- from creating jobs to protecting the environment to helping our veterans," Boxer wrote in an open letter to the mayor.
"So I am speaking to you now on a personal and professional level, and asking you to step down as mayor and get the help you need as a private citizen," Boxer wrote.
Filner, 70, a Democrat, has rejected numerous calls for his resignation. He is undergoing a two-week regiment of therapy to learn how to treat women with respect.
Some 14 women have accused Filner of making unwanted and unpleasant sexual advances, most during his terms in Congress but some since he was elected mayor in November.
His former director of communications, Irene McCormack Jackson, has filed a sexual harassment lawsuit seeking unspecified damages from Filner and the city.
"Bob, you have already hurt so many people," Boxer wrote. "To avoid hurting your victims and the people of San Diego more than you already have, you should step down immediately."
Filner is slated to return to City Hall on Aug. 19. He has promised to continue receiving counseling to change a long-term behavior pattern.
Filner and Boxer began their political careers in the activism of the 1960s: Boxer as a protester against the Vietnam War, Filner as a Freedom Rider in the civil rights movement.