The outfielder was plunked 19 times last year, tying him for first in the National League, and earlier this spring Arizona starter Daniel Hudson said he and his fellow pitchers had taken note.
Wednesday afternoon Upton was hit for the second straight day, this time by San Diego's Joe Wieland in the fourth inning.
In the seventh, after he had retired the first two batters of the inning, setup man David Hernandez plunked left-handed hitter Will Venable.
Home-plate umpire Alan Porter immediately issued warnings to both teams.
"Kind of," Hernandez said when asked if he was surprised by the warning. "I didn't really know that if I hit somebody, I was going to get a warning. I just know 'J' got hit. For me, in the spring, I've been trying to get the ball in to lefties. That's been a weakness for me. I got the ball in to the first lefty I faced. That's something I've got to work on."
And the pitch to Venable?
"I kind of spun off of it and yanked it," he said. "Got him."
Hernandez maintained there was no intent to hit Venable, but he did acknowledge that the D-backs pitchers were aware of how often Upton had been getting hit.
"You've got to keep a running tally in your head, that's about it," he said. "As a pitcher, you definitely have to protect your guys, but I was trying to go in and it got away and it hit him."
The D-backs and Padres play one more time this spring and then face each other 18 times during the regular season.