Guillen started in right field and had one ball hit to him, a looping single by Chone Figgins to lead off the game. He played defense again in the top of the second, but was replaced by pinch-hitter Ryan Freel in the bottom half.
Royals officials said Guillen went to the hospital because of "sudden right leg pain."
Guillen, who's hitting .245, fouled a ball off his left foot against Tampa Bay on Saturday and was going to be held out of Monday's game against Los Angeles before it was rained out. He played both games of Tuesday's doubleheader, driving in three runs.