He'll try to bounce back in the decisive home finale against the Texas Rangers on Wednesday.
Sale (10-1, 2.09 ERA) allowed 11 runs over 57 2-3 innings while going 5-1 in eight starts prior to giving up five and eight hits in six innings while not factoring in the decision of 10-8 win over Minnesota on Friday.
"Didn't really have command of anything," manager Robin Ventura told MLB's official website. "Just an off night for him."
It's easy for Ventura and the White Sox (55-59) to write off that effort from Sale, who still ranks among the major league ERA leaders and is 5-0 with a 2.22 ERA in eight starts since losing at home Detroit on June 12.
The left-hander posted a 3.48 ERA while winning his first three starts versus Texas (44-69), then allowed eight runs and four homers in seven innings of an 11-5 home loss to the Rangers on Aug. 23.
Adrian Beltre and Adam Rosales each hit two home runs off Sale, whom the White Sox hope can go deep and avoid some extended work by a bullpen that's allowed 29 runs and 39 hits over 13 1-3 innings of the last four games it's been needed. Designated hitter Adam Dunn accounted for one of those runs and two hits as he pitched the ninth on Tuesday.
Beltre's two-run homer in the first inning was one of five for the Rangers in Tuesday's 16-0 rout. Robinson Chirinos homered twice and J. P. Arencibia added one with four RBIs for Texas, which totaled 12 runs while losing its previous seven road contests.
The Rangers are 7-26 since last winning consecutive games June 27-28.
''We just kept putting runs on the board, and that's what we have to continue to do," manager Ron Washington said. "I just hope this is a reward for us to turn things around and we can get more consistent.''
Four of Beltre's seven hits in his last 29 at-bats against the White Sox have left the park.
After his turn in the rotation was skipped because of some knee soreness, Texas' Nick Tepesch (3-7, 4.84) returns to the mound looking to avoid a fourth straight losing decision as a starter. The right-hander is 0-3 with a 6.85 ERA in four starts since a 5-4 win over Minnesota on June 27.
Tepesch also took the loss in a 2-1, 14-inning defeat at Yankee Stadium on July 22 when he allowed a run and three hits in one-third of an inning.
He yielded three runs on two homers in six innings of a 5-1 defeat to Oakland in his most recent start July 26.
Tepesch gave up five runs and eight hits in 6 2-3 innings of a 5-2 loss to Chicago while opposing Sale on May 1, 2013.
Conor Gillaspie had two hits, including a home run versus Tepesch in that contest.
With two hits Tuesday, Gillaspie is batting .345 while hitting safely in all eight career games versus Texas.
Alejandro De Aza went 2 for 4 with a home run and double against Tepesch last May, but it's uncertain if he'll miss a second straight contest with a bruised knee.