Wainwright takes the mound as the visiting St. Louis Cardinals look to avoid a fifth straight loss to the Padres on Tuesday night.
One day after routing Washington 13-4, San Diego (21-23) got three hits from Chris Denorfia in a 4-2 victory over St. Louis, the team's third win in a row and fifth in seven games.
Denorfia is 6 for 13 during the winning streak while Will Venable has homered in each of the last two, giving him home runs in back-to-back games for the first time since Aug. 4 and 5, 2009.
The Padres, though, may have a tough time continuing their hot hitting with Wainwright (5-3, 2.51 ERA) on the mound.
The right-hander is 3-2 with a 0.97 ERA in five career starts versus San Diego, and Venable (4 for 16) and Chase Headley (2 for 12) have struggled against him.
However, Wainwright allowed five runs - though only two were earned - and walked four in six innings of a 6-4 loss Sept. 11 in his last game against the Padres. He'll be looking to bounce back from a so-so outing after giving up four runs - three earned - in six innings of a 5-2 loss to the New York Mets on Thursday.
''I made a couple mistakes over the plate that ended up costing us runs,'' Wainwright said. ''The ones they were supposed to hit, they hit. If I make my pitch, most of the time (the opposition doesn't) get hits.''
St. Louis (28-16) had a tough time at the plate in Monday's series opener, as Jon Jay had two of the team's four hits. The Cardinals have finished with fewer than five only six times this season.
San Diego, which has outscored St. Louis 24-11 while winning the last four meetings, will turn to Edinson Volquez to try and slow the Cardinals' offense again.
Volquez (3-4, 5.55) had gone 3-0 with a 2.49 ERA over his previous four starts before giving up five runs and walking four in five innings of a 6-2 loss to Washington on Thursday.
"It was my fault. I'm supposed to pitch seven, eight innings," said Volquez, who has walked 14 over his last four starts. "I walked a couple guys in the beginning of (innings). ... That's something I've got to stop doing."
The right-hander has had a difficult time versus the Cardinals in recent years, going 1-3 with a 6.60 ERA in his last six starts against them. Matt Holliday is 7 for 17 with two homers off Volquez.
It's unclear if St. Louis third baseman David Freese will be in the lineup for this contest after sitting out Monday. He received three stitches in his right thumb after getting spiked in Sunday's win over Milwaukee.
Ty Wigginton, batting .194, could start in Freese's place again.