Simmons, who has missed six games already this season because of the same injury, exited in the second quarter.
Nets coach Jacque Vaughn said Simmons was having some discomfort in the knee and asked to come out. He doesn't think Simmons will need another MRI but the team will see how he's feeling on Tuesday and is listing him as day-to-day for now.
"We'll check him day by day, see how he responds with a little treatment," he said, "see what it looks like (Tuesday)."
Vaughn does not think Simmons' latest knee setback is related to his back surgery over the summer.
"No, I think more so than anything the accumulation of games," Vaughn said. "He hasn't had this amount of accumulation of games over a period of a long time. Talked to the performance team about that. We were warned about that just as these games start to add up.
"His cumulative load as that begins to add up, it's really stretching him sometimes the amount of games we've just had with the minutes that he's played pretty high going into tonight's game."
Since returning to the floor after missing a Nov. 13 loss to the Los Angeles Lakers, Simmons has played his best basketball of the season -- averaging 10.5 points, 7 rebounds and 5.2 assists during November.
Simmons finished Monday's game with zero points, four rebounds and three assists in 12 minutes.
"When he's not out there, we don't have our point forward, or our point guard," Nets guard Kyrie Irving said, noting that he appreciated the training staff's cautious approach with Simmons. "Being able to initiate easy opportunities, push the ball in transition, so we'll definitely miss him in the lineup. Hopefully he comes back next game. If he's dealing with it, we just want him to come back as healthy as possible and we'll figure it out."
The Nets are already playing without big man Yuta Watanabe, who remains out because of a right hamstring strain. Vaughn said before the game that Watanabe had another MRI on his hamstring on Monday but that the results haven't returned yet.
Nets star Kevin Durant knows that if Simmons has to miss any more time the Nets will have to play an even smaller lineup without him.
"We've got to play smaller, he's one of our bigs out there," Durant said. "So I thought coach did a good job of trying to pick out the small lineup on the fly. We got to play a little faster and I think we all got to do a good job of gang rebounding, doing the little stuff when he's not out there.
"We have some practice in with him not being in the lineup and we was able to figure some stuff out, so something as drastic as this, him leaving in the (second) quarter, we was able to make that adjustment."