Simmons, who has already missed 11 games this season because of injury, exited in the third quarter but it is unclear exactly when he got hurt.
Playing on the second night of a back-to-back, Simmons struggled to make an impact during 20 minutes of action on Thursday, going 0-for-3 from the field, with seven assists, one rebound and three turnovers.
Nets forward T.J. Warren also exited the game midway though the fourth quarter with a left knee contusion.
Nets coach Jacque Vaughn said after the game it was still unclear whether Warren or Simmons would need to have an MRI on Friday.
Having done a good job recently of keeping the group's spirits high as they continue to deal with different injuries to key players, Nets guard Kyrie Irving said he would keep being consistent in his own approach.
"I can't control everyone's emotions day to day as much as I see myself as one of the leaders of our team," Irving said after scoring 40 points in Thursday's loss. "But what I can show is just a consistency to continue to work on off days and after the games and before the games and just continue to prepare at a very high level. Whoever's available for us to play will be available and just move onto the next game."
The Nets are playing without star forward Kevin Durant for at least a couple more weeks as he continues to rehab an MCL sprain in his right knee. Seth Curry missed Thursday's game because of right knee soreness. Now it's unclear whether Warren or Simmons will be available for Saturday's game against the New York Knicks.
The hits keep on coming for a Nets team that has dropped six of its last eight without Durant in the lineup.
"As much as I would love to sit up here and give you guys a nice diatribe of what it looks like in the future, I just don't know," Irving said. "T.J. being out, Ben being out, so we just got to take it one day at a time and just want those guys to get healthy and that's the most important thing. We just got to carry our own water right now. Chop wood, carry water."