Four came on one pitch in the sixth frame on Saturday, when Griffin offered up a grand slam to veteran catcher Henry Blanco, making his Mariners' debut, in a 4-0 A's loss, the club's sixth in nine tries vs. Seattle this year.
Oakland, which dropped its first series since May 13-15 against the Rangers having also lost Friday's opener, is 17-4 against all other AL West teams.
Perhaps because no other division foe can throw out both Felix Hernandez and Hisashi Iwakuma -- they of a combined 2.06 ERA -- in the same series. The A's have faced Hernandez twice this year and will go up against Iwakuma for a third time Sunday.
To this point, Oakland has scored just three runs total over 27 2/3 innings against these Mariners hurlers.
"We get those guys every time," manager Bob Melvin said. "I think that has a lot to do with it. We haven't scored a whole lot of runs."
Griffin matched Hernandez for five innings, stranding six runners before the start of an eventful sixth, jumpstarted by Kendrys Morales' leadoff base hit. One out later, Michael Morse doubled, leading Griffin to intentionally walk Michael Saunders and bring up Blanco, who had not hit a grand slam since 2000.
But the 41-year-old backstop needed to see just one pitch -- an 88-mph fastball -- to alter the game, sending it just inside of the left-field foul pole for a four-run lead the Mariners would never surrender.
It helped that they had Hernandez, who didn't give up a run in seven innings, on their side.
"I wanted to be aggressive," Blanco said. "He's trying to throw me a fastball to get ahead and I got him."
"It was one pitch today," Griffin said. "I was just trying to get weak contact, and Henry, I guess he was looking for a well-placed fastball and hit it and it went out. If you look at the video, I would've hit John [Jaso] right where he was set up. Up and in. It could've been a little more in maybe, but it was still a well-placed ball.
"That makes it easier to accept, but at the end of the day, it's four runs on one pitch, and when you're facing a guy like Felix, every run counts, even a little bit more you could say. It's tough to take that. Man, it's really frustrating."
Seattle's ace was his usual self on this day, limiting the A's to just five hits with eight strikeouts and one walk over seven shutout innings, marking the 10th time in 15 starts he's allowed one run or fewer.
"His stuff is better than most, so it's always tough going up against him," said John Jaso, who caught Hernandez in Seattle, including his perfect game. "That's typical. That's boring Felix. It's tough to get comfortable against him."
The A's did have a chance to strike first in the fifth, with Jed Lowrie leading off the inning with a double, advancing to third on a fly out and dashing for home on another, but Endy Chavez gunned him down at the plate.
"You gotta take a chance with Felix there," Melvin said. "That was our only opportunity to score a run right there."
"Trying to send Jed right there," Jaso added, "that's the kind of stuff you have to do against a guy like that."
Against Oakland, Hernandez has yet to surrender a run this season over 14 2/3 innings. In that time, he's allowed just eight hits next to 16 strikeouts and two walks. Even more, he's now 15-6 with a 2.60 ERA in 28 career starts vs. the A's, fanning 187 in 193 2/3 innings.
For Griffin, it was his first career lost against an American League West opponent, having entered the day 7-0 with a 2.39 ERA in 10 previous starts against division foes.
"One pitch can do it," he said. "He came up clutch for them right there. I'm kind of at a loss for words. It's really frustrating to go 5 1/3 scoreless and then give up a grand slam and get the next two outs. It's really frustrating. Hopefully, we're not talking about something like this again."