His White Sox went down, 8-7, in an 11-inning marathon and left Kansas City with two losses in two days.
The loss stung for a multitude of reasons. They've now lost four in a row to Kansas City this season and sit 3 1/2 games behind the American League Central Division leaders.
But for Guillen, his club's fourth straight loss stung for another reason.
"Players out there, they just, they want to take it for granted," Guillen said. "Well, they better be careful, they better be careful. I'm not afraid to move people, I'm not afraid to make changes."
The White Sox were 11-10 after beating Seattle on April 29. But after a five-game road trip to Texas and Kansas City, the White Sox are 12-14 and searching for some answers.
Two of those answers seemed to be right fielder Jermaine Dye and third baseman Josh Fields. They returned to the lineup Tuesday, having both missed games after being hit by pitches in Texas.
Fields and Dye helped the White Sox break out of a two-game offensive funk with home runs, but starter Gavin Floyd and a host of relievers couldn't hold down the Kansas City attack.
The White Sox and Royals traded punches all night, and for a while, Chicago seemed to be landing most of the bigger blows. The White Sox didn't even trail until Royals catcher John Buck provided the final punch of the evening in the bottom of the 11th. Buck singled off White Sox reliever Lance Broadway with the bases loaded, scoring Mitch Maier to give Kansas City its fourth win in a row.
Broadway took the loss as the White Sox wasted leads of 5-1 and 7-4, amassed by 16 hits.
"What's annoying is that the team gave me run support," said Floyd, who lasted six innings and took a no-decision after allowing six runs on six hits. "I was not able to keep [the Royals] a far distance away."
The White Sox, who used six pitchers in 11 innings, had plenty of opportunities to end their losing skid.
They threatened to break a 7-7 tie in the top of the 10th, but Royals reliever Jamey Wright stranded a runner at second base by striking out Jim Thome to end the inning.
That opportunity came after the White Sox had another chance to break the deadlock in the top of the ninth.
A.J. Pierzynski, who finished a home run shy of the cycle, tripled to left with one out. But this time, Wright struck out Alexei Ramirez and got Scott Podsednik to ground out to second.
But all that came after the White Sox pitching staff had already allowed leads to disintegrate.
"I think getting ahead of guys is very key for me, said Floyd, who combined with reliever Scott Thornton to blow a 7-4 lead in the sixth and seventh innings. Floyd allowed two runs in the sixth and Thornton gave up one in the seventh.
"Early on, I got ahead," Floyd said. "But then when we got a lead, I didn't attack them like I usually do."
The White Sox batters did their best to keep Chicago in front all night. After seeing their 5-1 lead shrink to 5-4 in the fourth inning, the White Sox added two more runs in the fifth. Dye led off the inning with a walk, moved to third on a single from Pierzynski, and scored on an RBI single by Ramirez. Pierzynski added the second run when he scored on a sacrifice fly from Podsednik.
The White Sox struck first, scoring a run in the top of the second, and Dye and Fields gave the White Sox a lift in the third. Fields hit a 391-foot home run to left to lead off the inning, and after Thome walked with one out, Dye belted a two-run homer to left to give the White Sox a 4-0 lead. The White Sox knocked around Royals starting pitcher Kyle Davies for six runs in five innings.
After pitching two scoreless innings, Floyd finally surrendered a run in the third when Royals second baseman Alberto Callaspo homered into the Kansas City bullpen in right field.
Carlos Quentin had an RBI single in the fourth, scoring Chris Getz.
But Floyd got pinched for three more runs in the fourth. With two men aboard, Royals DH Mike Jacobs blasted a 440-foot homer to center field, pulling the Royals to within one at 5-4.
After four straight losses, the White Sox return home to face the Tigers in a short two-game set. They need a win badly. And if you believe Guillen, they might need some changes.
"The way we played, just be careful with some changes," Guillen said. "We don't do the little things to win games, and I mean, when you don't do the little things to win games, you're not going to win that many games."