Lester will attempt to knot the series for the Sox, who were blanked by Chicago, 3-0, on Friday afternoon. The left-hander hasn't found a groove yet this season and is winless in his last four starts.
While victories have been scarce for Lester this year -- he's 3-4 with a 4.57 ERA -- strikeouts haven't been an issue. Lester fanned nine over seven innings in his last start, against the Nationals. When his cutter and curveball have movement, Lester is at his best.
"Like I've said before, when guys don't swing at the pitches you want them to, it's hard to strike them out," Lester said. "It's not something I'm trying for. The biggest thing is that walks are down. That's all I can control -- trying to execute pitch after pitch -- and if they swing and miss or if they take it, I deal with the result as we go. It's something I'm not worried about. I've never been worried about it. I just keep trying to throw strikes and get guys out as quick as we can."
Samardzija will try to find a feel for his split-finger fastball as the Cubs look to win back-to-back games for the second time in a week.
Samardzija was hit hard by the Twins in his last start, allowing a season-high eight runs over 3 2/3 innings. The right-hander is 5-4 with a 3.96 ERA in 12 starts this season, but he's 1-3 in his last six outings.
Cubs manager Dale Sveum was a coach with the Red Sox in 2004, when they won the World Series. Boston's only holdovers from that team are David Ortiz and Kevin Youkilis.
Sveum has tried to downplay the series between two of the oldest franchises in baseball, even though the Red Sox are visiting Wrigley Field for the first time since 2005.
"It's just another series," Sveum said. "Obviously, the fans and everybody know the Red Sox are in town; the Red Sox against the Cubs are two of the most historic teams in baseball on a weekend in one of the better parks in the country. The fact of the matter is we go about business the same way. We have to try to get better and win baseball games."
Red Sox: Nava near return to starting lineup
For a fifth straight game, Daniel Nava did not start in left field on Friday due to left hand soreness, but manager Bobby Valentine hopes Nava can start on Saturday.
Nava pinch-hit in the ninth inning on Friday, striking out against Cubs closer Carlos Marmol. He's the latest Boston player to miss time with an injury.
The Red Sox have 10 players on the disabled list. Youkilis returned on Friday after missing one game due to being hit by a pitch in the ribs.
All of the moving parts have left Valentine without a consistent lineup or roster.
"It's not very versatile, but the guys have made it more versatile," Valentine said. "I wouldn't say that it's necessarily roster versatility -- it's a couple of individuals who are going a little beyond the call of duty to give us the best chance of winning. I think it's real important to have individuals who are willing to do the right thing and help the team win."
The Red Sox are 2-3 in the five games Nava hasn't started since his injury. He is hitting .295 with 19 RBIs and a .425 on-base percentage this season.
Cubs: Valbuena filling in at third
Luis Valbuena will be Chicago's primary third baseman with Ian Stewart on the disabled list due to a sore left wrist.
Valbuena started at third for the second time in as many games on Friday. He was called up from Triple-A Iowa on Thursday and is 0-for-6 with an RBI in two starts.
"[We like] his defense and left-handed bat -- he can drive the ball," Sveum said. "We'll keep him in there. He was swinging the bat well down there. You try to keep that left-handed bat in the lineup as much as you can."
Valbuena hit .303 at Iowa but played second base mostly. He said that third is a more difficult position, especially when a right-handed hitter is in the batter's box.
"It's harder," Valbuena said. "You have to be ready every time."
The Red Sox lead the Major Leagues with 233 extra-base hits this season, including 157 doubles.
Cubs infielder Jeff Baker is 4-for-4 against Lester in his career.
Boston is 1-3 all time at Wrigley Field.