"I've got my hands full with the (swine) flu right now and I'm going to stick with that," the former governor and attorney-general of Arizona said on the "Fox News Sunday" program.
Napolitano has been floated as a possible name for President Barack Obama to name to the nation's highest court following Souter's announcement Friday that he plans to retire in June.
Pressed on whether she would accept the coveted job if asked by Obama, Napolitano said: "Listen, I think the president has many, many excellent choices before him and that's his choice to make."
Obama said he aims to have a replacement on the bench by the time the court begins anew in October, "someone with a sharp and independent mind and a record of excellence and integrity."
The former constitutional law professor is said to prefer a woman for the job. His spokesman Robert Gibbs said Obama was seeking "diversity of experience" in his nominee, and that a "rigorous" vetting process was underway.