Parker, 34, had an MRI after suffering the injury during the Spurs' 121-96 victory over the Houston Rockets on Wednesday night.
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With 8:43 left in the fourth quarter, Parker immediately clutched at his left knee after a driving floater over Patrick Beverley and collapsed to the court, where he lay motionless for several minutes.
He rose to his feet but was unable to put any pressure on his left leg to walk, so he was carried off the court by rookie guard Dejounte Murray and center Dewayne Dedmon.
Said coach Gregg Popovich after the game: "It's not good."
Houston will host Game 3 of the best-of-seven Western Conference semifinals on Friday night.
Earlier in the contest, Parker became the ninth player in NBA postseason history to reach 4,000 career points. Parker and LeBron James are now the league's only players to have scored 4,000 points and dished 1,000 assists in the postseason.
Parker missed 16 games during the regular season because of rest and various ailments, such as right knee soreness, a left quadriceps bruise, a left knee bruise, left foot pain and back stiffness.
The most likely candidate to receive first crack at replacing Parker in the lineup is veteran Patty Mills, who averaged 9.5 points per game and 3.5 assists during the regular season and contributed seven points on Wednesday against the Rockets. If Mills moves to the starting lineup, it is likely Manu Ginobili will serve as the primary backup.
Parker's absence also will lead to more minutes for Murray, as well as Kyle Anderson, a former college point guard, and Jonathon Simmons.
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