Parker played 10 minutes of the first half and missed his only two shots before departing. The Spurs originally said his return was uncertain, then announced after halftime that he wouldn't play.
San Antonio led 51-44 at halftime as it tried to eliminate the Portland Trail Blazers.
Parker left the game with 8:46 remaining in the second quarter. He headed back to the locker room followed closely by San Antonio general manager R.C. Buford and team physician, Dr. Paul Saenz.
There was no indication that Parker was injured before leaving the game.
Parker was averaging 23 points and 6.5 assists through the first four games after scoring 32 points in San Antonio's Game 7 victory over Dallas.
Parker missed 13 games this season, but none due to a hamstring injury.