Both could be ready for Wednesday night's opener of the AL division series against the Los Angeles Angels.
The Red Sox can use the power that Lowell and Drew bring to the plate and that Josh Beckett, recovering from an injured side muscle, uncorks from the mound, but think they have enough depth without them.
"We've been able to win 95 games without everyone healthy," manager Terry Francona said Monday about an hour before the team left Fenway Park for the airport and the cross-country journey to Anaheim for Game 1.
Lester was 16-6 and Matsuzaka 18-3.
"We love what Beckett can do and we respect what Beckett can do," Francona said Monday. "We're starting to get that feeling about Lester."
So the Red Sox expect strong performances from Lester and Matsuzaka.
"You want Josh Beckett to go for you," Kevin Youkilis said, "but to start up with Jon Lester and Dice-K isn't too bad either."
Francona said not much has changed since Sunday night when news of Beckett's injury surfaced.
"Although he does feel better, the idea would be for him to play catch [Tuesday] and have a side [session] on Thursday," he said.
Beckett pitched the opener of last year's first-round series against the Angels and was overpowering. He pitched a complete-game, four-hit shutout with eight strikeouts and no walks. The Red Sox won 4-0 and went on to sweep the three-game series, giving them nine straight postseason wins over the Angels.
Los Angeles managed a total of four runs in the series and a .192 batting average.
But the Angels were hobbled by injuries to outfielders Gary Matthews Jr., Vladimir Guerrero and pitcher Bartolo Colon, while outfielder Garret Anderson was hampered by conjunctivitis that led to a swollen right eye.
The Red Sox hope they can be more successful coping with injuries.
Drew played just two games in September because of a strained lower back but responded well to getting three at-bats in the opener of Sunday's day-night doubleheader.
"J.D. did OK," Francona said. "Today was optional and he felt good enough to be able to participate in [batting practice], which was really a good sign."
Lowell has been slowed by a sore left hip that affects him much more while fielding. He should know more after fielding grounders Tuesday in Anaheim.
Will he play Wednesday night?
"It depends on tomorrow," Lowell said. "I've got to see how I'm moving defensively but I'm anticipating something good."
Lowell was the MVP when Boston won its second World Series in four years last season and hit .274 with 17 homers and 73 RBIs while being limited to 113 games this season.
"Having Mike Lowell out of the lineup is tough for us defensively and offensively," Youkilis said. "He's one of our top players (but) we're very comfortable with those guys stepping up" as replacements.
Drew played in 109 and hit .280 with 19 homers and 64 RBIs. When David Ortiz spent all of June on the disabled list, Drew hit .337 with 12 homers and 27 RBIs in 26 games.
If Lowell doesn't play, the Red Sox likely would move Youkilis to third and start Mark Kotsay at first. If Drew is out, Kotsay could play right field or Jacoby Ellsbury could play there with Coco Crisp taking his starting spot in center field.
The Angels won 100 games. The Red Sox won 95, one less than last season when they won the AL East, and finished two games behind Tampa Bay in the division.
Lowell isn't surprised Los Angeles is favored.
"Considering everything we went through and having our record almost the same" as last year is encouraging, he said. "Being a wild card, I don't think is as disappointing as if we had won 85 games.
"I don't think anyone cares whether you won the year before or not on how they're going to approach you. They want to beat you and eliminate you so they can move on."
If the Red Sox can gain a split on the road, and barring a health setback for Beckett, they would have their postseason star on the mound at Fenway Park on Sunday.
Lowell missed 19 games with a strained right oblique in his side after going on the disabled list Aug. 13. Beckett's injury, suffered on the 40th pitch of a bullpen session on Friday, doesn't seem as serious.
"It depends on how severe it was in the first place. They're saying that kind of immediately he felt a little better," Lowell said. "Josh has proven he's such a good postseason pitcher that you want him there as many times as possible.
"But we also want him healthy and being able to compete at the level that he's used to."