"Can't win 'em all," O'Sullivan said through a grin, having fallen to 3-1 in a duel with veteran right-hander Gavin Floyd. "I made some good pitches, made some bad pitches. The last couple innings, the ball started to ride up on me, and they got a lot of fly balls.
"My whole philosophy is you can't hit a ground ball out of the park."
Paul Konerko also homered for Chicago, which goes for a sweep on Thursday behind southpaw John Danks. The Angels will counter with Ervin Santana.
"They're going to be angry tomorrow, and they're going to want to play well against us," White Sox catcher A.J. Pierzynski said. "So we've got to go out and battle, and hopefully John goes out and gives us a good start, and we can put up some good runs against Santana."
An offense that was scorching hot for three weeks has come to a screeching halt on the South Side. After a committee of pitchers handled the first game, Floyd frustrated the Angels for eight-plus innings, and Thome was launched homers against O'Sullivan in the fourth inning and veteran Darren Oliver in the sixth.
"I watched him do that a lot growing up," said O'Sullivan, whose home in El Cajon, Calif., is found outside San Diego.
It was the Angels who struck first. Bobby Abreu singled with two out in the first and rambled home when right fielder Jermaine Dye misplayed Vladimir Guerrero's line drive into a three-base error, the ball deflecting off his glove and rolling to the fence.
Floyd (9-6) settled into a groove and silenced the Angels' bats, getting out of three innings with double-play grounders.
"He never gives in, even when he's behind in the count," said catcher Mike Napoli, whose sixth-inning double was one of six Angels hits. "I saw a lot of cutters. Even the double I hit was on a cutter."
Cut to ribbons through eight innings, the Angels finally got Floyd out of the game in the ninth on singles by Guerrero and Juan Rivera. But Matt Thornton took care of the final three outs with Kendry Morales' fly ball scoring pinch-runner Reggie Willits.
"He pitched deep in the game, a terrific game," Angels manager Mike Scioscia said of Floyd.
Kendry Morales, Guerrero and Erick Aybar banged into double plays to end the fourth, sixth and seventh innings, respectively.
"Three guys hit the ball on the screws with guys on and they turned double plays," Scioscia said. "I thought our at-bats were OK. We've been attacking and very strong in those [run-scoring] areas for a while. It's not going to be there every night."
Scioscia liked what he saw of his own pitcher, the competitive 21-year-old Irish kid with the full windup and darting fastball.
"Sean O'Sullivan pitched a lot better than the linescore showed," Scioscia said, the numbers in question being five innings, four earned runs and six hits with three strikeouts and no walks. "He got a couple of pitches up, and those guys got hits when they needed them."
Coming off a near-perfect game, a one-walk no-hitter for Triple-A Salt Lake in Sacramento eight days ago, O'Sullivan was imperfect -- but not bad at all in the judgment of his receiver.
"I thought he did good enough to get a win out of it," Napoli said. "He's definitely a guy who's not scared to be out there. I have a good feeling with him on the mound. I'm confident he's going to give us a good effort -- good command, good mound presence."
O'Sullivan was sailing along with a one-hitter when Thome struck with two outs in the fourth, his arcing drive reaching the seats.
"Fastball away," O'Sullivan said. "I left it up a little bit, and he put a good swing on it."
Jayson Nix's two-out single flared into right -- no luck there for the big Irishman -- gave the Sox the lead in the fifth, scoring Pierzynski, who had led off with a double.
O'Sullivan departed after Gordon Beckham doubled leading off the sixth and Dye's single put runners on the corners.
Thome greeted Oliver with his 20th homer of the season, another opposite-field shot.
Konerko's eighth-inning blast to left, his 21st, came with Brian Fuentes making his first appearance in eight days.