The Twins ace gave up six runs over his seven innings in what was his final home start of the season.
The loss was his ninth at the Metrodome this season, a new career high, and brought his record at home this season to 5-9 with a 3.76 ERA over 15 starts.
Yet it hasn't been just his home record which has shown Santana to be a bit more fallible this season.
One of the biggest differences for Santana in '07 has been his penchant for giving up home runs. Santana gave up three on Friday night, bringing his season total to 33 homers allowed, which ranks first in the American League.
"I think you saw Johan get the ball up just a little bit too much," manager Ron Gardenhire said. "When he gets the ball up, it'll go just as far with him throwing as anyone else. And I think Johan will tell you that tonight he didn't make enough adjustments to the hitters and he left the ball out and over the plate too many times."
The first of the three homers came in the first inning. Santana's ERA in the first frame rose to 6.47 when Josh Fields hit a solo shot to give Chicago a 1-0 lead.
Solo homers have made up the majority of Santana's dingers this season, but it was a big multi-run blast that proved most costly on Friday night. In the fifth inning, Santana gave up a two-out single to Jerry Owens and then walked Fields. Jim Thome followed with a three-run shot over the left-field wall for his 31st home run of the season to put Chicago up, 5-3.
"Every time you walk somebody, the last thing you want to do is have that guy score," Santana said. "And that has been one of the toughest things throughout the whole season, is letting guys score on a walk. That's something I need to improve on."
Fields came into the game as one of Chicago's hottest hitters, batting .500 (8-for-16) with two home runs and seven RBIs over his last four games. And he proved tough on Santana all night. The White Sox left fielder followed up the walk with another solo homer in his next at-bat in the seventh.
It's not often that Santana gives up two homers to the same hitter in an outing, but Fields credited his fortune Friday night to luck.
"Honestly, against that guy, you just close your eyes and swing," Fields said.
Santana almost made it back-to-back two-out homers in the seventh. Following Fields, Thome appeared to hit what was his second homer of the game, but Twins left fielder Lew Ford reached over the wall to rob Thome for the inning's final out.
"I didn't think it was gonna go as far as it did," Ford said. "It just kept going. I've learned from the best out there, Torii [Hunter]. I just tried to go up there and make the catch."
The final two home runs given up by Santana erased what had been an early Twins lead. The club tagged White Sox starter Mark Buehrle (10-9) for three runs in the third inning.
Minnesota would add one more when Nick Punto delivered an RBI triple in the sixth. Punto's 2-for-4 performance at the plate raised his season average to .214 and also extended his hitting streak to a season-high seven games.
Much has been made about the barrage of homers for Santana this season, but the pitcher hasn't been too concerned.
"Sometimes it's about not guessing right or leaving a pitch up, and I don't really worry about it," Santana said. "Like I've said in the past, I'd rather give up a homer than just give up hits and doubles and going crazy out there. Unfortunately, you don't want to give it up like tonight, where you have a pretty good chance to win and one of those homers changed the whole game.
"That's the way it is. I don't really try to think much about other things. I just try to go back out there and do my job."
And at least one of his opponents agrees with Santana that those home run numbers don't really mean the Twins ace has changed.
"He's the same," Thome said. "Any time you go against him, you hope you get a ball to hit and when you get it, you can't miss it. When we face him, we know we have to bring our 'A' game. We had a good night, that's all it was."