Right-hander Bannister left the game in the second inning with right shoulder fatigue. Guillen, back in the lineup as designated hitter, left in the sixth inning because of soreness in his right hamstring tendon.
Bannister gave up three runs to the Oakland A's in the first inning and then left with one out in the second inning.
The first four A's batters reached base and three runs were home before Bannister got three straight outs. After Cliff Pennington led off the second inning with an infield popup, Bannister was visited on the mound by assistant athletic Frank Kyte and acting manager John Gibbons.
Bannister was replaced by Yasuhiko Yabuta and then trotted into the Royals' dugout.
Guillen had been out of the lineup for 37 games with a ligament tear in his right knee. Batting sixth as the DH, Guillen struck out and grounded out in his only two at-bats.
John Buck batted for Guillen in the sixth.
Dick Kaegel is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.