The Cardinals try to bounce back from an anemic offensive showing Saturday against Travis Wood.
St. Louis (69-52) lost Friday's opener 7-0 after dropping two of three at home to the Cubs last weekend.
"We've played some of our best baseball against them," Chicago manager Dale Sveum said. "Even in some of the ballgames we've lost, we've played good ball and come up on the short end. We've played these guys really well."
The Cubs are 7-7 against the Cardinals but 12-28 against the rest of the NL Central.
Chicago (53-68), however, isn't the only team giving St. Louis problems. The Cardinals have lost six of nine and own the NL's second-worst record since July 26 at 7-15.
Highly touted prospect Kolten Wong made his major league debut for the Cardinals, going 0 for 3 with a strikeout. Manager Mike Matheny had the 22-year-old playing second base and moved regular second baseman Matt Carpenter to third. Struggling David Freese was relegated to the bench but is expected to be back in the lineup against Wood (7-9, 3.00 ERA).
Yadier Molina also will likely return after a day off following an 0-for-5 return from the disabled list. The NL MVP candidate is batting .429 with nine RBIs against the Cubs this season and is 5 for 9 in 2013 matchups with Wood.
Beltran is also excelling in those matchups, batting .392 with six doubles against Chicago and going 3 for 10 versus the left-hander.
Wood yielded two runs and four hits in a season-high eight innings against Cincinnati on Monday but was saddled with a 2-0 loss. It was his 20th quality start - tying him for second in the majors - and the third time in four outings he allowed two runs or fewer.
Although Wood is enjoying a solid season, it hasn't led to many wins, with the Cubs losing 10 of his last 13 starts.
Friday's victory snapped a four-game losing streak for Chicago and seven-game skid at Wrigley Field. Nate Schierholtz drove in three runs while Junior Lake and Anthony Rizzo each scored twice for the Cubs, who had been shut out in two of their previous three games.
Rizzo is partly to blame for Chicago's offensive woes, batting .140 in his last 13 contests. He is 3 for 23 in his last six games against St. Louis and 1 for 9 lifetime versus Joe Kelly (3-3, 3.14).
Kelly was a little shaky against Chicago on Sunday, giving up four runs and six hits in 5 1-3 innings and not earning a decision in an 8-4 victory. He walked two, and is averaging 4.1 walks per nine innings over his last seven outings.
"I would like to go a little deeper, I can't do that when I start walking guys like that," the right-hander told the Cardinals' official website.
Kelly was 3-0 with a 0.78 ERA over his previous four starts. That stretch began at Wrigley on July 12, when he allowed a run and three hits over 5 1-3 innings of a 3-2 victory.
Wood is 1-1 with a 3.26 ERA in three starts against the Cardinals this season.