Rockets officials are still trying to determine if Motiejunas needs back surgery.
Motiejunas, who averaged career highs in points (12.0) and rebounds (5.9) per game, was injured in late March. But after a game at New Orleans, where he scored 21 points and grabbed eight rebounds in 36 minutes, he reported more problems with his lower back.
"He's one of the guys we definitely went to," said Rockets coach Kevin McHale. "He was able to get on the low box and if our offense got slowed down we were able to play though D-Mo, especially late. He puts pressure on the defense and we're going to miss him. He put in a lot of hard work into it and he worked really hard since he's been here.
"It's too bad, I feel really bad for him. He's one of the guys who never misses a day, he's in the gym every day on off days, he's in shooting and he really works on his game hard and we'll miss him and he's going to miss playing, too. The kid loves to play basketball."
Rockets GM Daryl Morey had said there was a hope Motiejunas would return before the end of the regular season, but with his back not improving it was determined to end his season with just five games remaining.
Motiejunas, who started 62 of 71 games, becomes the latest Rockets player to be lost either for the season or for an extended period of time.
The Rockets missed starting center Dwight Howard for 38 games due to various injuries, including a two-month stretch where he endured swelling in his right knee.
Howard is back with the Rockets but isn't playing in back-to-back games and is on a minutes restriction.
Starting point guard Patrick Beverley is out for the season after undergoing left wrist surgery to repair ligament damage.
With Motiejunas done for the season, coach Kevin McHale will employ smaller lineups at times and could extend the minutes of backup forward/center Joey Dorsey, who is averaging 12.5 minutes per game.
In addition to Dorsey getting more minutes, 6-8 rookie forward Kostas Papanikolaou, who hasn't played since Feb. 21 because of a sprained right ankle, suffered during a practice, is expected to see some playing time in Thursday's game against the Spurs.
"We're going to do what we've been doing and that's mix and match," McHale said.
Motiejunas had emerged in his third NBA season as a reliable player for McHale. He was averaging career highs in minutes (28.7) and field goal percentage (.504). Per 100 possessions, Motiejunas was averaging 20.9 points and 10.3 rebounds this season.