Tulowitzki, who leads the majors with a .356 batting average this season, exited Friday's contest in San Francisco in the ninth inning after he limped past first base on a base hit.
X-rays on Tulowitzki's foot were negative, and Rockies manager Walt Weiss told reporters that the three-time All-Star is dealing with a sprained toe.
The Rockies have not released a timetable for how long the injury will sideline Tulowitzki, who leads the team in virtually every offensive category. Josh Rutledge started at shortstop Saturday against the Giants.
Tulowitzki, 29, is batting .356 with 17 home runs and 43 RBIs this season.
The Rockies, who rallied for five ninth-inning runs to win Friday's series opener, already are without All-Star outfielder Carlos Gonzalez (finger), young third baseman Nolan Arenado (finger) and veteran outfielder Michael Cuddyer (shoulder).