Matsuzaka was hammered by the Tampa Bay Rays last Tuesday for eight runs and eight hits in just 4 2/3 innings, dropping him to 9-5 on the season, while raising his earned run average to 4.70.
"Lack of command caught up with him and kind of caught up in a hurry," Red Sox manager Terry Francona said of his starting pitcher.
Matsuzaka has faced the Mariners seven times and is 2-1 against them with a 3.65 ERA.
Boston can only hope its Japanese hurler gives the type of effort Jon Lester provided it with in the opener on Monday. Lester pitched eight impressive innings, leading the Red Sox to a 5-1 win.
Lester (17-8) allowed just one run on three hits and three walks, striking out 12 for the Red Sox, who won for the fourth time in seven games. The lefty, who is 6-1 over his last seven starts, also struck out 10 or more for the fourth straight outing, a career-best.
"I was able to locate a fastball and get ahead," Lester said. "That's big for any pitcher, getting ahead and being able to do what you want to with it. You get a couple runs on the board and you can sit back a little bit and minimize damage. It makes things easier, takes pressure off you so you can go out there and pitch."
Ryan Kalish added a two-run homer, while Lars Anderson hit his first career double and knocked in a run.
Chone Figgins had two hits, and Casey Kotchman drove in the lone run for Seattle, which has lost five straight. Doug Fister (5-12) was victimized for five runs, six hits and a walk in 7 1/3 frames to take the loss.
"I thought Fister was good tonight," said Mariners manager Daren Brown. "You take away the second inning, after that, he only gave up one hit going into the eighth. I thought he pitched well, just a couple of mistakes the one inning. Other than that I thought he was solid."
Heading to the hill for the Mariners this evening will be left-hander Luke French, who is 4-5 on the year with a 3.90 ERA. French absorbed the loss on Wednesday in Oakland, as he allowed four runs and seven hits in 5 1/3 innings.
This will be his first-ever appearance against the Red Sox.
Boston is 5-3 against Seattle this season.