Lowell, who has a sore hip, was hitless in four at-bats and moved gingerly on defense in Game 1, which the Red Sox won, 4-1.
Instead, manager Terry Francona had Kevin Youkilis moving from first base to thirde and Mark Kotsay at first against Los Angeles Angels right-hander Ervin Santana. Kotsay is seven for 18 against Santana. In another change from Game 1, Alex Cora started over Jed Lowrie at shortstop for the Red Sox.
On Thursday's off day, Lowell sounded like a guy who expected to play every game.
"I don't think I put myself in a position to play one game," he said.
Francona said Lowell's injury – he has a torn labrum in his left hip – had not worsened and suggested Lowell could return in Game 3 against Angels' lefty Joe Saunders.
"With Mikey Lowell, that was a hard one for us," he said. "It's pretty obvious he's hurting. … Getting to that decision for me, that was the toughest. I know he wanted to play, which would be a shock for him not to.
"I thought I had an obligation to do the best I can do to make a decision. I don't think I'll ever feel we're a better team with Lowell not in the lineup."
Desperately seeking offensive improvement, Angels manager Mike Scioscia benched right fielder Gary Matthews Jr. and replaced him with Juan Rivera. After missing most of 2007 because of a broken leg and starting slowly as the odd-man out in the Angels outfield, Rivera was better in the second half of 2008, but still batted only .206 with runners in scoring position.