Political observers predict a tight race between two sitting city council members, Democrat David Alvarez and Republican Kevin Faulconer, the Los Angeles Times said.
Early in the race, Faulconer, 47, held a significant lead on his younger Latino opponent but recent polling indicates a surge in support among the Latino and other minority communities has seen Alvarez, 33, pull even.
"It may be a late evening for poll watchers," said Vince Vasquez of the National University System Institute for Policy Research.
Despite a significant enrollment advantage for Democrats -- who hold a majority on the city council and all the city's congressional districts -- Republicans have traditionally fared well in mayoral races in San Diego.
Filner, who resigned last year after allegations from multiple women surfaced he had sexually harassed them, was the first Democrat to lead the city in two decades.
Tuesday's winner will take office March 3 and serve out the remaining 33 months of Filner's term.