Sale gave up six runs on six hits and a walk in 2 2/3 innings.
Xavier Nady drove in the first Padres' run with a two-out single in the first. San Diego added single runs in the second and third.
Andrew Cashner pitched three shutout innings for the Padres. He gave up two hits and no walks, and struck out three.
Cody Decker, a non-roster catcher, homered for San Diego in the eighth off White Sox lefty David Purcey.
Padres: Cashner threw very few sliders -- just five, according to manager Bud Black. But the hard-throwing right-hander was pleased with how it worked.
Cashner said the most important thing "was getting it in the zone around where my four-seam (fastball) lives and my sinker lives, because it's the same arm slot. Just getting it around the plate is the main focus for me."
White Sox: Sale, who threw 41 of his 59 pitches for strikes, said he was working more on his breaking ball in his second spring start. The ace left-hander gave up six hits, walking one and striking out one.
"I got to my pitch count, but you still want to go out there and do well," Sale said. "I didn't have any control with my breaking ball. It wasn't very sharp. I threw more hanging breaking balls today than I did all year."
Chicago reliever Nate Jones threw two 15-pitch bullpen sessions on Wednesday and said he's ready to go. Jones, who has not yet appeared in a game after a gluteal strain sustained early in camp, will probably throw again on the side this weekend before a potential spring debut. Another potential closer for the White Sox, Matt Lindstrom, said he was happy with his workout. Lindstrom has been sidelined with an oblique strain since Friday and, like Jones, is taking the long view of recovery with Opening Day nearly four weeks away.
Paul Konerko celebrated his 38th birthday, playing first base and getting a single in two at-bats. He was presented with a cake by second baseman Gordon Beckham before the team's morning workout. Among the well-wishers for the White Sox veteran was Padres first-base coach Jose Valentin, who was a teammate of Konerko's in Chicago from 2000-04.
BACK TO BUSINESS
Adam Dunn has put Hollywood behind him and is back to his regular job as White Sox first baseman-DH. He had his first hit of the spring, a single, and was 1 for 2.
"It was an experience for sure. There were a lot of pretty significant people everywhere you went," said Dunn, who was an investor in the "Dallas Buyers Club," a movie that won three Academy Awards Sunday night. Dunn also appeared briefly in the film.
"It's pretty exciting," he said. "Not bad for the first movie to go home with three of them."
When Dunn returned to camp on Tuesday, he was greeted by a red carpet leading to his clubhouse locker, complete with theater ropes and giant Oscar cut-outs.
THOME TAKES A LOOK
Former White Sox slugger Jim Thome, a special assistant to general manager Rick Hahn, got his first look at rookie first baseman Jose Abreu this week. Thome -- who hit 612 home runs in his career -- likes what he sees.
"From all the reports he's got a ton of passion," Thome said. "He wants to do well. He looks like he's going to be a really good player. He looks very good. Like the other young guys, they need to play and get that experience."
Abreu had the day off on Wednesday.