Last year, New York lost two of three games against Florida in its final series of the season, including a defeat in the finale that gave Philadelphia the NL East title.

In the opener of this series with the Marlins (83-76), the Mets (88-72) lost 6-1 on Friday night to fall two games behind the NL East-leading Phillies and one behind Milwaukee in the wild-card race with two games left.

Philadelphia can clinch the division title with a win or a New York loss.

"We really, really have put ourselves in a tough spot," Mets manager Jerry Manuel said. "We're the only ones to blame. We had opportunities and we didn't get it done."

In the middle game of last year's series with the Marlins, the Mets got an outstanding performance from John Maine in a 13-0 win. But Maine (shoulder) hasn't been healthy enough to start, putting New York's rotation in a bind.

So Manuel will be forced to hand the ball to Santana (15-7, 2.64 ERA) on three days' rest.

"I just told Jerry, whatever we have to do, I'll be fine with that. It's all about winning," Santana said.

Santana has never gone three days between regular-season starts. He did so for Minnesota in the 2004 AL playoffs, allowing one run in five innings in a 6-5 loss to the New York Yankees.

Santana, though, has been impressive in four career starts against the Marlins, going 4-0 with a 2.49 ERA and a .208 opponent batting average.

The left-hander threw a career-high 125 pitches in Tuesday night's 6-2 victory over the Cubs. He allowed two runs and seven hits while striking out 10 in eight innings.

Santana is 7-0 with a 2.00 ERA in his last 13 starts, but he has had wins taken away due to an inconsistent Mets bullpen. New York's lineup fizzled Friday but its bullpen was also partly to blame, giving up three runs in three innings.

If games ended after eight innings, the Mets would have entered Friday with an eight-game lead over the Phillies in the NL East, according to STATS, LLC.

Meanwhile, five Marlins pitchers combined to give up one unearned run Friday. They'll now send Ricky Nolasco (15-7, 3.55 ERA) to the mound.

Nolasco is 5-1 with a 2.82 ERA in his last 11 starts, but 2-4 with a 6.92 ERA in eight starts and two relief appearances against the Mets.

In his last outing, the right-hander gave up three runs and six hits while striking out five in six innings as Florida lost 7-5 to Cincinnati on Monday.

Nolasco has gotten a total of 17 runs to work with in his last three starts, and the Marlins are coming off another solid game at the plate.

Josh Willingham homered and Hanley Ramirez had four hits to lead Florida. With 125 runs, Ramirez tied his own team record set last season.

The Marlins, who have scored 15 runs en route to winning their last two games, are relishing the chance to end the Mets' season for the second straight year.

"Obviously, we are not going to play on (Wednesday)," Florida manager Fredi Gonzalez said. "This is as big as it gets for us."