Pierce's frustrating start in his first season in Brooklyn now includes a nondisplaced fracture of the third metacarpal of his shooting hand.
Coach Jason Kidd said he did not know when Pierce injured his hand, but in a news release the team said he was hurt Friday in the first half of a loss at Houston.
The swingman played only 15 minutes before Kidd benched four of his starters, including Pierce, for the entire second half of the 114-95 defeat.
Pierce, 36, did not play in the Nets' last game, a 97-88 win in Memphis on Saturday.
Williams has already been ruled out for Tuesday's game against Denver and is considered doubtful for Thursday's game against the Knicks.
This season, the Nets (5-12) have lost a total of 37 games due to injury to six players. Kidd has had to use seven different starting lineups as Joe Johnson has been the only starter to start every game this season.
Pierce has struggled in his first season as a Net, but Brooklyn will miss the veteran's leadership and experience on the court. Pierce is shooting only 36.8 percent and 26.8 percent from behind the 3-point arc while averaging 12.4 points and 4.9 rebounds. Pierce is on pace for career lows in shooting percentages and scoring average in his 16-year career.
Alan Anderson started in place of Pierce against Memphis last Saturday and should continue to start while Pierce is sidelined.
"Injuries are a part of the game," Kidd said. "You just hope that there are speedy recoveries. And for the guys in that locker room that can play, I believe in each one of those guys and that we can find a way to win until we do get whole."
The Nets acquired Pierce and Garnett in a summer blockbuster trade that put the Nets into title-contender status. But the NBA's highest payroll has provided little bang for the buck, struggling with injuries and a lack of chemistry.
The Nets have lost 10 of their last 13 games with two of the victories coming in the last four games.
Pierce's injury will keep him out of his first New York showdown against the Knicks on Thursday. And Pierce will miss what was supposed to be his first game against his old team, the Celtics, next Tuesday.
After missing a potential game-tying 3-pointer in a loss to the Lakers last week, Pierce said the Nets have to keep things together while they wait for injured players to return.
Now the Nets have to do that without Pierce.
"We are still learning," Pierce said of learning how to win short-handed last week. "Hopefully we learn before it's too late, before we are completely out of the playoff mix.
"But we still have time," Pierce added. "We will be a dangerous team. Right now we got to be able to hold down and get some wins just to gain some confidence. We can't wait on guys to get healthy. We have to get the job done now. I have to play better. A lot of us have to play better."