Moustakas aggravated a previous injury in the sixth inning of Monday night's 6-3 loss to the Tigers.
"Moose is done," Royals manager Ned Yost said. "When he slid into second base, he re-aggravated his groin so with two games left, that's probably going to be it for him."
Moustakas was pulled out of Sunday's game at Cleveland because of the injury. Although hurt in the sixth inning on Monday night, he didn't leave the game until the ninth.
That apparently leaves the Royals without the starters at both corners of the infield, because first baseman Eric Hosmer also is likely to miss the final two games against the Tigers. He's been out since Thursday with a slight tear or moderate strain in his right rotator cuff sustained at Detroit. Hosmer was re-examined on Monday.
"I saw the doctor and he pretty much confirmed the strain and stuff," he said. "He likes how it's rehabbing but the strength is still not 100 percent there. So he's saying it's just a matter of day to day and just try to get it as strong as possible."
Shortstop Alcides Escobar sustained a bruised right shoulder on Thursday and missed all three weekend games at Cleveland. He also was re-examined after returning to Kansas City and played Monday night.
Escobar must be OK. He singled in his first at-bat and made a spectacular fielding play with a long throw to first base in the fourth inning.