Ponds, the Big East preseason player of the year, ranks third in the league in scoring at 20.6 points per game. He is first in assists (6.0) and steals (2.7) and was one of 25 players in the country selected to the midseason watch list for the Wooden Award this week.
Bryan Trimble Jr. started in place of Ponds, who watched quietly from the bench in sweat pants and a red polo shirt.
"Anytime you take your best player off the team, it has an effect,'' coach Chris Mullin said. "I thought we played OK. A little passive, I thought.''
Mullin said Ponds is day-to-day.
"We've just got to play through,'' the coach added.
The school said Ponds initially was injured at Georgetown on Jan. 5, when he scored 37 points during an overtime victory. He played through the problem and had 23 points Tuesday night in a 76-71 loss at defending national champion Villanova.
Ponds had started all 16 games this season. St. John's went 1-2 without him last season.
St. John's (14-3, 2-3 Big East) dropped its second straight game since moving into the AP Top 25 for the first time in four years.
It marked DePaul's first win against a ranked team in nearly three years.
Information from The Associated Press contributed to this report.