Sale was able to throw strikes over his 2 2/3 innings of work, with 41 of his 59 pitches in the zone. When he did work around the plate, the Padres connected for six runs on six hits.
San Diego scored four runs in the first inning on singles from Everth Cabrera, Xavier Nady and Kyle Blanks, with Nady's scoring Cabrera. That shot up the middle was followed by Nick Hundley's opposite-field, three-run shot to right.
The Padres tallied single runs in the second and third on fielder's-choice grounders before Sale exited with two outs and two on. It wasn't the sort of results he was looking for, but Sale was more interested in the work than the runs allowed.
"We are here for a reason. It's to prepare yourself," Sale said. "You still want to do well and have success. But I'm definitely not losing any sleep tonight over this one.
"April and May comes around, June and July, something like that happens, that's when it eats at you. We are here to get our work in and results are secondary to that."
Andrew Cashner, who could get the Opening Day starting nod for San Diego, as Sale figures to have with the White Sox, produced work and results in Wednesday's victory. The right-hander allowed singles to Conor Gillaspie and Adam Dunn over three innings, striking out Gordon Beckham twice and fanning Marcus Semien once.
"The breaking ball was maybe the best it's been since 2012," Cashner said. "I started throwing my spike again and got the depth and bite I like. I threw some good changeups and broke some bats on some inside fastballs."
Paul Konerko singled in two at-bats, coming through on his 38th birthday. Cabrera and Rymer Liriano had two hits apiece for the Padres. Cody Decker crushed a two-run homer of White Sox reliever David Purcey in the eighth inning.
Dylan Axelrod shut down the Padres for three scoreless innings, allowing two hits and a walk while striking out three.
Up next: John Danks' scheduled Cactus League debut last Saturday turned into a simulated game in the batting cages because of inclement weather. So the Mariners will be his first official trip to the mound with actual opposition in Thursday's 2:05 p.m. CT split-squad action at Camelback Ranch, airing on a live whitesox.com video webcast. Reliever Mitchell Boggs is also on the pitching schedule in Glendale.
Chris Beck, a rising pitching prospect in the White Sox system, gets the start in Surprise against the Royals at 2:05 p.m., live on Gameday Audio.