Santana exited after being hit in the second inning and is day to day with a bruise. Manager Mike Scioscia said Santana, who is in line to be the No. 3 or 4 starter, could miss a start without being set back for the season.
Santana said he felt a little pain, but he wasn't worried. While icing the shoulder, he said no X-ray was planned. Santana pitched a no-hitter against the Cleveland Indians on July 27 and he finished last season 11-12 with a 3.38 ERA.
"Everything will be OK," he said.
Pujols hit a three-run home to left field and a solo shot to center. The three-time NL MVP signed a 10-year, $254 million deal with the Angels in December after he played 11 seasons with the St. Louis Cardinals.
"I try to just put a good swing on it all the time," Pujols said. "I'm not sitting out there trying to hit the ball out of the park. I'm just trying to hit the ball back to the middle and let the ball get deep and try to make good swings every day, whatever I have to do to help this ballclub and this organization win.
"I know it's spring training. The games probably don't count, but you still need to take the game serious," he added.
"We hope we're going to see that often this year," Scioscia said. "It's great to see him getting comfortable in the box."
After the line drive struck Santana, he was able to field the ball and throw to first to retire Alexei Ramirez. The Angels' staff checked on Santana and then he was replaced by Eddie McKiernan.
"We'll see tomorrow," Santana said.
Santana allowed a run and a hit, struck out two and walked one in 1 1/3 innings in his second start of spring training.
"I felt very good," Santana said. "The ball was coming out good."
Chris Sale allowed five runs in 4 1/3 innings for the White Sox. He gave up seven hits and struck out two. Sale, who is transitioning from a reliever to a starter, has allowed eight runs in 7 1/3 innings.
"That's unacceptable on every level, I don't care who you are," Sale said. "By no means am I going to go home and kick myself in the rear, but I'm disappointed with what happened today. At the same time, there are positives with this. I had some good innings."
Sale hit Pujols with a pitch in the first inning. Pujols hit a three-run home run off Sale the next time he faced him.
"A hitter like him, he's arguably the best in the game," Sale said. "He proved a couple innings later if you're going in, you better get it in."
Manager Robin Ventura reaffirmed his confidence in Sale.
"He's still got great stuff," Ventura said. "He's going to be in there."
Flowers hit a solo homer, his second of the spring, off McKiernan. Kendrick hit his second home run, a two-run shot off Anthony Carter. Dunn also hit his second of the spring, a two-run drive.
As a precaution, White Sox closer candidate Jesse Crain didn't pitch because of a slight strain of his right oblique. .Dunn was back in the lineup as the designated hitter after sitting out Tuesday with a stiff neck. .The White Sox optioned right-handed pitcher Gregory Infante to Triple-A Charlotte, reassigned catcher Damaso Espino, right-handed pitchers Brian Omogrosso and Jacob Petricka and outfielders Brandon Short and Delwyn Young to the minor league camp and
added infielder Tyler Saladino to major league camp. Ventura said he wanted to see Saladino, who started at second base and hit second.