CHICAGO -- Friday's series opener of the Crosstown Classic, Part II should have belonged to Mark Buehrle.

The White Sox left-hander battled flu-like symptoms and still allowed just two runs in seven innings of work against the rival Cubs.

But as has been the case seemingly countless times throughout the 2007 season, a White Sox starting pitcher's hard work went in vain. The offense floundered and the bullpen collapsed, this time in a 5-1 loss to the Cubs before a sellout crowd of 39,046 at U.S. Cellular Field.

Instead of Buehrle's heroics, it was Cubs starter Carlos Zambrano's performance that stole the show. Zambrano struck out a season-high 12 hitters and allowed just three hits over eight innings, impressing White Sox manager Ozzie Guillen.

"He was tough," Guillen said of Zambrano, who threw 74 of his 113 pitches for strikes. "Last two outings he threw ... We were watching the game before he faced us, and he was throwing the ball better than early in the season. He caught the White Sox at the right time.

"We didn't swing well and he threw well. You're not going to win too many games with three hits."

Zambrano (8-6) retired the first 10 White Sox hitters, including seven of the first nine on strikeouts. His 12 strikeouts on the afternoon also matched his career high.

"He was throwing every pitch for a strike, a 3-2 slider, splitty, whatever," said White Sox third baseman Josh Fields, who struck out once swinging and once looking. "You looked out on the mound and if he threw a ball to get to 3-2 with his fastball, you could tell he was confident to throw whatever he wanted for a strike."

The White Sox lone offensive breakthrough against the Cubs' right-hander came in the seventh, when Paul Konerko hit a solo home run into the left-center-field seats, his 12th of the season and 250th in a White Sox uniform. But beyond Konerko's one powerful swing, the Sox offense had no answer for Zambrano or Cubs closer Ryan Dempster, who hurled a perfect ninth inning.

Guillen's crew fell behind early as Buehrle (4-4) struggled out of the gate. Alfonso Soriano led off the ballgame with a solo home run to left field, and three batters later, Aramis Ramirez made it 2-0 with an opposite-field home run.

Perhaps the biggest blow in the first inning, however, came on a play in which the White Sox recorded an out.

Immediately following Soriano's home run, Mike Fontenot hit a sinking liner into center field. Darin Erstad, who was activated from the disabled list prior to the ballgame, made a diving catch to rob Fontenot of a hit. On the play, however, Erstad re-aggravated his left ankle sprain and was taken out of the game before he was scheduled to come up to lead off the bottom of the first.

After the rough first inning, Buehrle was dominant. In his final six innings of work, the southpaw allowed no runs and just two hits, while striking out three. After he was removed from the game, Buehrle was taken to the locker room, where he vomited and began to suffer dehydration as a result of the flu.

"He was pretty good," Pierzynski said of Buehrle. "Take away that first inning, and he was really good. It's a shame that Zambrano was about as good as I've ever seen him."

The White Sox (29-40) stayed within striking distance until the ninth. But the bullpen, as it has done so many times in 2007, could not keep the game close. The Cubs (33-39) rallied for three runs in their final at-bat against a trio of White Sox relievers -- Nick Masset, Ryan Bukvich and Matt Thornton.

"It's scary," said Guillen of his woeful relievers. "I've never felt this scared in my life. I said in the seventh inning, I hope it starts raining right now and we stop the game for a little while.

"I don't have any other choice. I believe in the guys I'm bringing into the thing. The guys have good enough stuff, they're just not getting it done."

The late-inning breakdown pushed the bullpen ERA to 8.27 over the last 39 games. The White Sox also lost for the 20th time in 25 games and fell to 11 below .500 for the first time since May 29, 2001.

"If [Buehrle and Jon Garland] pitched last year the way they are pitching this year, they would have 10 to 12 wins right now," said Guillen, supported by Buehrle's 10 quality starts in 14 appearances this season.

The White Sox still hold a 30-28 advantage in the overall series against the Cubs, although the Cubs have taken three of four from them this season.